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Publications of Edward D. Levin    :chronological  alphabetical  combined listing:

%% Journal Articles   
@article{fds316075,
   Author = {Levin, ED and Rezvani, AH and Xiao, Y and Yenugonda, VM and Brown, ML and Kellar, KJ},
   Title = {Nicotinic treatments not only for tobacco, but also other
             addictions},
   Journal = {Biochemical Pharmacology},
   Volume = {97},
   Number = {4},
   Pages = {635-635},
   Publisher = {Elsevier BV},
   Year = {2015},
   Month = {October},
   ISSN = {0006-2952},
   url = {http://dx.doi.org/10.1016/j.bcp.2015.08.040},
   Doi = {10.1016/j.bcp.2015.08.040},
   Key = {fds316075}
}

@article{fds316106,
   Author = {Bailey, J and Levin, E},
   Title = {The neurobehavioral toxicity of FireMaster 550® in
             zebrafish ( Danio rerio ): Chronic developmental and acute
             adolescent exposures},
   Journal = {Neurotoxicology and Teratology},
   Volume = {49},
   Pages = {118-118},
   Publisher = {Elsevier BV},
   Year = {2015},
   Month = {May},
   ISSN = {0892-0362},
   url = {http://dx.doi.org/10.1016/j.ntt.2015.04.064},
   Doi = {10.1016/j.ntt.2015.04.064},
   Key = {fds316106}
}

@article{fds316096,
   Author = {Levin, ED},
   Title = {Age and sex differences in starting nicotine
             self-administration in early, mid or late adolescence vs.
             adulthood: Cause and effect relationships determined in a
             rat model},
   Journal = {Neurotoxicology and Teratology},
   Volume = {49},
   Pages = {140-140},
   Publisher = {Elsevier BV},
   Year = {2015},
   Month = {May},
   ISSN = {0892-0362},
   url = {http://dx.doi.org/10.1016/j.ntt.2015.04.128},
   Doi = {10.1016/j.ntt.2015.04.128},
   Key = {fds316096}
}

@article{fds316116,
   Author = {Hall, BJ and Cauley, M and Kiany, A and Burke, DA and Levin,
             ED},
   Title = {Low dose tobacco smoke extract exposure during development
             causes long-term behavioral dysfunction in
             rats},
   Journal = {Neurotoxicology and Teratology},
   Volume = {49},
   Pages = {121-122},
   Publisher = {Elsevier BV},
   Year = {2015},
   Month = {May},
   ISSN = {0892-0362},
   url = {http://dx.doi.org/10.1016/j.ntt.2015.04.073},
   Doi = {10.1016/j.ntt.2015.04.073},
   Key = {fds316116}
}

@article{fds316105,
   Author = {Oliveri, A and Levin, E},
   Title = {Early-life exposure to organophosphate flame retardants
             alters behavior in adult zebrafish: A comparison with
             organophosphate pesticides},
   Journal = {Neurotoxicology and Teratology},
   Volume = {49},
   Pages = {130-130},
   Publisher = {Elsevier BV},
   Year = {2015},
   Month = {May},
   ISSN = {0892-0362},
   url = {http://dx.doi.org/10.1016/j.ntt.2015.04.096},
   Doi = {10.1016/j.ntt.2015.04.096},
   Key = {fds316105}
}

@article{fds274205,
   Author = {Rezvani, AH and Levin, ED},
   Title = {Assessment of pregnenolone effects on alcohol intake and
             preference in male alcohol preferring (P)
             rats.},
   Journal = {Eur J Pharmacol},
   Volume = {740},
   Pages = {53-57},
   Year = {2014},
   Month = {October},
   ISSN = {0145-6008},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000304806000362&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Abstract = {Neuroactive steroids can modulate a variety of
             neurobehavioral functions via the GABAergic system. This
             study was conducted to determine the importance of the
             neurosteroid pregnenolone on the regulation of alcohol
             intake. The effects of acute and chronic administration of
             pregnenolone on alcohol intake were assessed in alcohol
             preferring (P) rats. The rats were injected i.p. with the
             vehicle or pregnenolone (25, 50 or 75 mg/kg) and their
             alcohol and water intake were recorded at 2, 4, 6 and 24 h.
             Also, the chronic effects of 50 mg/kg (i.p.) pregnenolone on
             alcohol intake were determined. Our results show that
             although the main effect of i.p. injection of pregnenolone
             in reducing alcohol intake was not quite significant
             compared with the vehicle, pregnenolone at 75 mg/kg
             significantly (P<0.025) reduced alcohol intake. Regarding
             alcohol preference, acute administration of pregnenolone
             both at 50 mg/kg (P<0.05) and at 75 mg/kg (P<0.025)
             significantly reduced alcohol preference. In chronic
             experiments pregnenolone given for 10 consecutive days did
             not show a significant effect on alcohol intake and alcohol
             preference. Overall, although pregnenolone given i.p.
             acutely and significantly reduced alcohol intake and
             preference, the fact that chronic treatment did not show an
             effect diminishes its promise to be considered for the
             treatment of alcoholism. However, its profile of effects
             might be different in human alcoholics.},
   Doi = {10.1016/j.ejphar.2014.07.003},
   Key = {fds274205}
}

@article{fds316110,
   Author = {Zhang, C and Bailey, JM and Oliveri, AN and Frazier, J and Delarosa, A and Crosby, E and Janardhan, S and Mackinnon, S and Levin, ED and Cole,
             GJ},
   Title = {LONG-TERM BEHAVIORAL EFFECTS OF EMBRYONIC ETHANOL EXPOSURE
             IN ZEBRAFISH},
   Journal = {Alcoholism, Clinical and Experimental Research},
   Volume = {38},
   Pages = {176A-176A},
   Publisher = {WILEY-BLACKWELL},
   Year = {2014},
   Month = {June},
   ISSN = {0145-6008},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000337523700705&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Key = {fds316110}
}

@article{fds316107,
   Author = {Cauley, M and Burke, D and Hall, BJ and Seidler, FJ and Slotkin, TA and Levin, ED},
   Title = {Sex-selective interaction of prenatal nicotine with neonatal
             chlorpyrifos on novel object recognition in
             rats},
   Journal = {Neurotoxicology and Teratology},
   Volume = {43},
   Pages = {88-89},
   Publisher = {Elsevier BV},
   Year = {2014},
   Month = {May},
   ISSN = {0892-0362},
   url = {http://dx.doi.org/10.1016/j.ntt.2014.04.043},
   Doi = {10.1016/j.ntt.2014.04.043},
   Key = {fds316107}
}

@article{fds316104,
   Author = {Burke, D and Levin, ED},
   Title = {Nicotinic α4β2 antagonist treatment attenuates impairments
             in radial-arm maze repeated acquisition caused by
             dizocilpine in rats},
   Journal = {Biochemical Pharmacology},
   Volume = {86},
   Number = {8},
   Pages = {1231-1231},
   Publisher = {Elsevier BV},
   Year = {2013},
   Month = {October},
   ISSN = {0006-2952},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000326007000039&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Doi = {10.1016/j.bcp.2013.08.047},
   Key = {fds316104}
}

@article{fds316095,
   Author = {Rezvani, AH and Xiao, Y and Brown, ML and Paige, MA and Yenugonda, VM and Kellar, KJ and Levin, ED},
   Title = {DESENSITIZATION OF A4 beta 2 NICOTINIC RECEPTORS ATTENUATES
             ALCOHOL INTAKE AND PREFERENCE IN ALCOHOL PREFERRING P
             RATS},
   Journal = {Alcoholism, Clinical and Experimental Research},
   Volume = {37},
   Pages = {247A-247A},
   Publisher = {WILEY-BLACKWELL},
   Year = {2013},
   Month = {June},
   ISSN = {0145-6008},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000318998301130&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Key = {fds316095}
}

@article{fds316093,
   Author = {Yenugonda, VM and Xiao, Y and Levin, ED and Rezvani, AH and Tran, TT and Al-Muhtasib, N and Wells, C and Slade, S and Johnson, JE and Kong, H-S and Dakshanamurthy, S and Tomita, Y and Liu, Y and Paige, MA and Kellar, KJ and Brown, ML},
   Title = {Design, synthesis, and characterization of picomolar
             selective a4b2 nicotinic acetylcholine receptor
             inhibitors},
   Journal = {Abstracts of Papers of the American Chemical
             Society},
   Volume = {244},
   Pages = {1 pages},
   Publisher = {AMER CHEMICAL SOC},
   Year = {2012},
   Month = {August},
   ISSN = {0065-7727},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000324621805663&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Key = {fds316093}
}

@article{fds316076,
   Author = {Yen, J and Donerly, S and Levin, E and Linney, E},
   Title = {Differing Effects of 3 Organophosphates (Chlorpyrifos,
             Diazinon and Parathion) on Developing Zebrafish Nervous
             System},
   Journal = {Neurotoxicology and Teratology},
   Volume = {33},
   Number = {4},
   Pages = {509-510},
   Publisher = {Elsevier BV},
   Year = {2011},
   Month = {July},
   ISSN = {0892-0362},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000294527900059&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Doi = {10.1016/j.ntt.2011.05.062},
   Key = {fds316076}
}

@article{fds316102,
   Author = {Rezvani, AH and Robinson, E and Eisenberg, L and Levin, ED and Bonaventure, P and Motley, T and Lovenberg, TW and Heilig, M and Thorsell, A and Cippitelli, A},
   Title = {EFFECTS OF A NOVEL, SELECTIVE BRAIN NPY Y2 RECPTOR ANATONIST
             JNJ-31020028, ON ALCOHOL CONSUMPTION, RELAPSE AND ANXIETY IN
             RATS},
   Journal = {Alcoholism, Clinical and Experimental Research},
   Volume = {35},
   Number = {6},
   Pages = {68A-68A},
   Publisher = {WILEY-BLACKWELL},
   Year = {2011},
   Month = {June},
   ISSN = {0145-6008},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000290804300230&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Key = {fds316102}
}

@article{fds316108,
   Author = {Rezvani, AH and Lumeng, L and Li, TK and Xiao, Y and Brown, ML and Paige,
             MA and McDowell, BE and Rose, JE and Kellar, KJ and Levin,
             ED},
   Title = {NICOTINE SELF-ADMINISTRATION IN SELECTIVELY-BRED ALCOHOL
             PREFERRING (P) RATS: NICOTINIC INVOLVEMENT},
   Journal = {Alcoholism, Clinical and Experimental Research},
   Volume = {34},
   Number = {6},
   Pages = {18A-18A},
   Publisher = {WILEY-BLACKWELL PUBLISHING, INC},
   Year = {2010},
   Month = {June},
   ISSN = {0145-6008},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000278107200032&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Key = {fds316108}
}

@article{fds316091,
   Author = {Levin, ED and Hampton, D and Xiao, Y and Kellar, KJ},
   Title = {Sazetidine-A, a nicotinic desensitizing agent, decreases
             nicotine self-administration in rats},
   Journal = {Biochemical Pharmacology},
   Volume = {74},
   Number = {8},
   Pages = {SMA43-SMA44},
   Publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
   Year = {2007},
   Month = {October},
   ISSN = {0006-2952},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000250188900096&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Key = {fds316091}
}

@article{fds316101,
   Author = {Levin, ED and Linney, E and Slotkin, TA},
   Title = {Complementary zebrafish and rat models of developmental
             neurobehavioral toxicity: The case of organophosphate
             pesticide exposure},
   Journal = {Neurotoxicology and Teratology},
   Volume = {29},
   Number = {3},
   Pages = {406-406},
   Publisher = {Elsevier BV},
   Year = {2007},
   Month = {May},
   ISSN = {0892-0362},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000247746900043&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Doi = {10.1016/j.ntt.2007.03.038},
   Key = {fds316101}
}

@article{fds316078,
   Author = {Levin, ED},
   Title = {Nicotinic treatment for both symptomatic relief and
             attenuation of cognitive decline with aging and Alzheimer's
             dementia.},
   Journal = {Neurotoxicology},
   Volume = {27},
   Number = {6},
   Pages = {1162-1162},
   Publisher = {ELSEVIER SCIENCE BV},
   Year = {2006},
   Month = {December},
   ISSN = {0161-813X},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000243211300069&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Key = {fds316078}
}

@article{fds316099,
   Author = {Levin, ED and Roegge, C and Timofeeva, O and Seidler, FJ and Slotkin,
             TA},
   Title = {Low dose early postnatal diazinon exposure causes impaired
             working memory on the radial-arm maze in rats during
             adulthood.},
   Journal = {Neurotoxicology},
   Volume = {27},
   Number = {6},
   Pages = {1165-1165},
   Publisher = {ELSEVIER SCIENCE BV},
   Year = {2006},
   Month = {December},
   ISSN = {0161-813X},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000243211300075&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Key = {fds316099}
}

@article{fds316117,
   Author = {Roegge, C and Timofeva, O and Seidler, F and Slotkin, TA and Levin,
             ED},
   Title = {Persisting effects of early postnatal diazinon exposure on
             emotional reactivity in rats},
   Journal = {Neurotoxicology and Teratology},
   Volume = {28},
   Number = {6},
   Pages = {709-709},
   Publisher = {Elsevier BV},
   Year = {2006},
   Month = {November},
   ISSN = {0892-0362},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000243168100018&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Doi = {10.1016/j.ntt.2006.09.015},
   Key = {fds316117}
}

@article{fds316077,
   Author = {Levin, ED and Bencan, Z and Cerutti, DT},
   Title = {Assessing stress in zebrafish: Anxiolytic effects of
             nicotine},
   Journal = {Neurotoxicology and Teratology},
   Volume = {28},
   Number = {6},
   Pages = {709-710},
   Publisher = {Elsevier BV},
   Year = {2006},
   Month = {November},
   ISSN = {0892-0362},
   url = {http://dx.doi.org/10.1016/j.ntt.2006.09.016},
   Doi = {10.1016/j.ntt.2006.09.016},
   Key = {fds316077}
}

@article{fds316092,
   Author = {Levin, ED},
   Title = {Cholinergic involvement in neurocognitive function: From
             zebrafish to humans.},
   Journal = {Neurotoxicology},
   Volume = {27},
   Number = {5},
   Pages = {892-893},
   Publisher = {ELSEVIER SCIENCE BV},
   Year = {2006},
   Month = {September},
   ISSN = {0161-813X},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000240408800072&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Key = {fds316092}
}

@article{fds316111,
   Author = {Rezvani, AH and Levin, ED},
   Title = {Nicotine-antipsychotic drugs interaction and sustained
             attention in rats},
   Journal = {The International Journal of Neuropsychopharmacology},
   Volume = {9},
   Pages = {S146-S146},
   Publisher = {CAMBRIDGE UNIV PRESS},
   Year = {2006},
   Month = {July},
   ISSN = {1461-1457},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000239495500566&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Key = {fds316111}
}

@article{fds316089,
   Author = {Levin, ED},
   Title = {Developing nicotinic therapy for cognitive impairment of
             schizophrenia and aging-related dementia},
   Journal = {The International Journal of Neuropsychopharmacology},
   Volume = {9},
   Pages = {S126-S126},
   Publisher = {CAMBRIDGE UNIV PRESS},
   Year = {2006},
   Month = {July},
   ISSN = {1461-1457},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000239495500494&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Key = {fds316089}
}

@article{fds316087,
   Author = {Levin, ED},
   Title = {Clozapine effects on memory function are reversed by
             hippocampal damage},
   Journal = {Neuropsychopharmacology},
   Volume = {30},
   Pages = {S197-S197},
   Publisher = {NATURE PUBLISHING GROUP},
   Year = {2005},
   Month = {December},
   ISSN = {0893-133X},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000233442100513&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Key = {fds316087}
}

@article{fds316114,
   Author = {Levin, ED and Rezvani, AH},
   Title = {Adolescent rats show differential effects of nicotine and
             alcohol relative to adults.},
   Journal = {Alcoholism, Clinical and Experimental Research},
   Volume = {28},
   Number = {5},
   Pages = {175A-175A},
   Publisher = {LIPPINCOTT WILLIAMS & WILKINS},
   Year = {2004},
   Month = {May},
   ISSN = {0145-6008},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000221549301009&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Key = {fds316114}
}

@article{fds316090,
   Author = {Weiser, M and Levin, ED and George, TP and Newhouse, PA and Leonard,
             S},
   Title = {Nicotinic receptor modulation of attention: An endophenotype
             for therapeutic drug development},
   Journal = {Biological Psychiatry},
   Volume = {55},
   Pages = {152S-152S},
   Publisher = {ELSEVIER SCIENCE INC},
   Year = {2004},
   Month = {April},
   ISSN = {0006-3223},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000220755300529&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Key = {fds316090}
}

@article{fds316079,
   Author = {Levin, ED and Blackwelder, WR and Glasgow, HB and Burkholder, JM and Moeller, PR and Ramsdell, JS},
   Title = {Learning impairment caused by infusion of a toxin produced
             by Pfiesteria piscicida into the hippocampus of
             rats.},
   Journal = {Toxicological Sciences},
   Volume = {72},
   Pages = {71-71},
   Publisher = {OXFORD UNIV PRESS},
   Year = {2003},
   Month = {March},
   ISSN = {1096-6080},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000181518500347&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Key = {fds316079}
}

@article{fds316088,
   Author = {Swain, H and Donerly, S and Chrysanthis, E and Yacsin, K and Linney, E and Levin, ED},
   Title = {A zebrafish model for studying the neurobehavioral impacts
             of developmental chlorpyrifos exposure.},
   Journal = {Toxicological Sciences},
   Volume = {72},
   Pages = {129-129},
   Publisher = {OXFORD UNIV PRESS},
   Year = {2003},
   Month = {March},
   ISSN = {1096-6080},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000181518500630&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Key = {fds316088}
}

@article{fds316086,
   Author = {LEVIN, ED and TORRY, D},
   Title = {Nicotine effects on memory performance},
   Journal = {Effects of Nicotine on Biological Systems
             Ii},
   Pages = {329-335},
   Publisher = {BIRKHAUSER VERLAG},
   Editor = {Clarke, PBS and Quik, M and Adlkofer, F and Thurau,
             K},
   Year = {1995},
   Month = {January},
   ISBN = {3-7643-5083-0},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:A1995BC71W00043&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Key = {fds316086}
}


%% Papers Published   
@article{fds347048,
   Author = {Hawkey, A and Pippen, E and White, H and Kim, J and Greengrove, E and Kenou, B and Holloway, Z and Levin, ED},
   Title = {Gestational and perinatal exposure to diazinon causes
             long-lasting neurobehavioral consequences in the
             rat.},
   Journal = {Toxicology},
   Volume = {429},
   Pages = {152327},
   Year = {2019},
   Month = {November},
   url = {http://dx.doi.org/10.1016/j.tox.2019.152327},
   Abstract = {Diazinon is a widely-used organophosphate pesticide.
             Pulsatile exposure to diazinon during neonatal development
             has previously been shown cause long-term neurobehavioral
             impairments in rats. However, the effects of chronic low
             concentration exposures during perinatal development remain
             unclear. This experiment evaluated such effects in
             Sprague-Dawley rats by implanting osmotic pumps in breeder
             females prior to conception (N = 13-15 litters per
             condition) which then delivered chronic, zero order kinetic
             low-level infusions of 0, 114 or 228 ug/day of diazinon
             throughout pregnancy. One male and one female from each
             litter was assessed with a battery of behavioral tests that
             continued from four weeks of age into adulthood. Litter was
             used as the unit of variance for the analysis of variance
             test of significance, with sex as a within litter factor.
             Diazinon treatment condition was the between subjects factor
             and time or sessions were repeated measures. Chronic
             diazinon exposure from pre-mating until the neonatal period
             caused a significant (p < 0.05) increase in percent of
             time spent on the open arms of the elevated plus maze, an
             index of risk-taking behavior. Gestational and lactational
             diazinon exposure also caused a significant (p < 0.05)
             degree of hyperactivity in the Figure-8 apparatus during
             adolescence, specifically affecting the early part of the
             hour-long test session. This effect had dissipated by the
             time the rats reached adulthood. Diazinon exposure also
             caused a significant impairment in novel object recognition,
             a test of cognitive function. Offspring exposed to 228
             ug/day diazinon (p < 0.05) showed significantly less
             preference for the novel vs. familiar object than controls
             during the first five minutes of the novel object
             recognition test.},
   Doi = {10.1016/j.tox.2019.152327},
   Key = {fds347048}
}

@article{fds345840,
   Author = {Willette, BKA and Nangia, A and Howard, S and DiPalma, D and McMillan,
             C and Tharwani, S and Evans, J and Wells, C and Slade, S and Hall, BJ and Rezvani, AH and Levin, ED},
   Title = {Acute and chronic interactive treatments of serotonin 5HT2C
             and dopamine D1 receptor systems for decreasing nicotine
             self-administration in female rats.},
   Journal = {Pharmacol Biochem Behav},
   Volume = {186},
   Pages = {172766},
   Year = {2019},
   Month = {November},
   url = {http://dx.doi.org/10.1016/j.pbb.2019.172766},
   Abstract = {A variety of neural systems are involved in the brain bases
             of tobacco addiction. Animal models of nicotine addiction
             have helped identify a variety of interacting neural systems
             involved in the pathophysiology of tobacco addiction. We and
             others have found that drug treatments affecting many of
             those neurotransmitter systems significantly decrease
             nicotine self-administration. These treatments include
             dopamine D1 receptor antagonist, histamine H1 antagonist,
             serotonin 5HT2C agonist, glutamate NMDA antagonist,
             nicotinic cholinergic α4β2 partial agonist and nicotinic
             cholinergic α3β4 antagonist acting drugs. It may be the
             case that combining treatments that affect different neural
             systems underlying addiction may be more efficacious than
             single drug treatment. In the current study, we tested the
             interactions of the D1 antagonist SCH-23390 and the
             serotonin 5HT2c agonist lorcaserin, both of which we have
             previously shown to significantly reduce nicotine
             self-administration. In the acute interactions study, both
             SCH-23390 and lorcaserin significantly reduced nicotine
             self-administration when given alone and had additive
             effects when given in combination. In the chronic study,
             each drug alone caused a significant decrease in nicotine
             self-administration. No additive effect was seen in
             combination because SCH-23390 given alone chronically was
             already highly effective. Chronic administration of the
             combination was not seen to significantly prolong reduced
             nicotine self-administration into the post-treatment period.
             This research shows that unlike lorcaserin and SCH-23390
             interactions when given acutely, when given chronically in
             combination they do not potentiate or prolong each other's
             effects in reducing nicotine self-administration.},
   Doi = {10.1016/j.pbb.2019.172766},
   Key = {fds345840}
}

@article{fds345740,
   Author = {Levin, ED and Wells, C and Yao, L and Guo, W and Nangia, A and Howard, S and Pippen, E and Hawkey, AB and Rose, JE and Rezvani,
             AH},
   Title = {Chronic memantine decreases nicotine self-administration in
             rats.},
   Journal = {Eur J Pharmacol},
   Volume = {861},
   Pages = {172592},
   Year = {2019},
   Month = {October},
   url = {http://dx.doi.org/10.1016/j.ejphar.2019.172592},
   Abstract = {Neurobehavioral bases of tobacco addiction and nicotine
             reinforcement are complex, involving more than only
             nicotinic cholinergic or dopaminergic systems. Memantine is
             an NMDA glutamate antagonist used to improve cognitive
             function in people with Alzheimer's disease. Glutamate may
             be an important component of the reinforcing effects of
             nicotine, so memantine was evaluated as a potential smoking
             cessation aid. Two studies were conducted with adult female
             rats, one testing acute effects of memantine over a range of
             doses for changing nicotine self-administration and the
             other testing the chronic effects of memantine to reduce
             nicotine self-administration. Acute memantine injections
             slightly, but significantly, increased nicotine
             self-administration in a dose-related manner. In contrast,
             chronic memantine treatment significantly reduced nicotine
             self-administration. During the first day of memantine
             administration in the chronic study, nicotine
             self-administration was significantly elevated replicating
             the acute study. Starting in the second week of treatment
             there was a significant reduction of nicotine
             self-administration relative to controls. This was seen
             because memantine treatment prevented the increase in
             nicotine self-administration shown by controls. There even
             continued to be a memantine-induced lowered nicotine
             self-administration during the week after the cessation of
             memantine treatment. Memantine or other drugs affecting NMDA
             glutamate receptors may be useful aids to smoking cessation.
             Full efficacy for reducing nicotine self-administration was
             seen as the NMDA drug treatment is given chronically.
             Importantly, the effect persisted even after treatment is
             ended, indicating the high potential for NMDA glutamate
             receptors to impact nicotine addiction.},
   Doi = {10.1016/j.ejphar.2019.172592},
   Key = {fds345740}
}

@article{fds343374,
   Author = {Hawkey, AB and White, H and Pippen, E and Greengrove, E and Rezvani, AH and Murphy, SK and Levin, ED},
   Title = {Paternal nicotine exposure in rats produces long-lasting
             neurobehavioral effects in the offspring.},
   Journal = {Neurotoxicol Teratol},
   Volume = {74},
   Pages = {106808},
   Year = {2019},
   Month = {July},
   url = {http://dx.doi.org/10.1016/j.ntt.2019.05.001},
   Abstract = {Studies of intergenerational effects of parental chemical
             exposure have principally focused on maternal exposure,
             particularly for studies of adverse neurobehavioral
             consequences on the offspring. Maternal nicotine exposure
             has long been known to cause adverse neurobehavioral effects
             on the offspring. However, paternal toxicant exposure has
             also been found to cause neurobehavioral toxicity in their
             offspring. Recent work suggests that paternal nicotine
             exposure can have epigenetic effects, although it remains
             unclear whether such changes lead to neurobehavioral
             effects. In the current study, we investigated the effects
             of paternal nicotine exposure on neurobehavioral development
             of their offspring. Male Sprague-Dawley rats were exposed to
             0 or 2 mg/kg/day nicotine (sc) for 56 consecutive days
             with two consecutive 2ML4 osmotic minipumps. Following
             treatment, these males were mated with drug-naïve female
             rats. Offspring of both sexes were tested in a behavioral
             battery to assess locomotion, emotional function and
             cognition. Paternal nicotine exposure did not impact
             offspring viability, health or growth. However, behavioral
             function of the offspring was significantly altered by
             paternal nicotine exposure. Male offspring with paternal
             nicotine exposure exhibited locomotor hyperactivity in the
             Figure-8 apparatus when tested during adolescence. When
             retested in adulthood and regardless of sex, offspring of
             the nicotine exposed father showed significantly reduced
             habituation of locomotor activity over the course of the
             session. Compared to controls, female offspring of
             nicotine-exposed fathers showed significantly reduced
             response latency in the radial arm maze test. In addition to
             locomotor hyperactivity, the offspring of nicotine-exposed
             fathers also showed significantly diminished habituation in
             the novel object recognition test. These results indicate
             that chronic paternal nicotine exposure can impact the
             behavior of offspring, producing locomotor hyperactivity and
             impaired habituation.},
   Doi = {10.1016/j.ntt.2019.05.001},
   Key = {fds343374}
}

@article{fds342565,
   Author = {Levin, ED and Hawkey, AB and Hall, BJ and Cauley, M and Slade, S and Yazdani, E and Kenou, B and White, H and Wells, C and Rezvani, AH and Murphy, SK},
   Title = {Paternal THC exposure in rats causes long-lasting
             neurobehavioral effects in the offspring.},
   Journal = {Neurotoxicol Teratol},
   Volume = {74},
   Pages = {106806},
   Year = {2019},
   Month = {July},
   url = {http://dx.doi.org/10.1016/j.ntt.2019.04.003},
   Abstract = {Developmental neurotoxicity of a wide variety of toxicants
             mediated via maternal exposure during gestation is very well
             established. In contrast, the impacts of paternal toxicant
             exposure on offspring neurobehavioral function are much less
             well studied. A vector for paternal toxicant exposure on
             development of his offspring has been identified. Sperm DNA
             can be imprinted by chemical exposures of the father. Most
             but not all of the epigenetic marks in sperm are
             reprogrammed after fertilization. The persisting epigenetic
             marks can lead to abnormal genetic expression in the
             offspring. We have found that paternal delta-9-tetrohydrocannabinol
             (THC) exposure in rats causes changes in methylation of
             sperm (Murphy et al., 2018). This is similar to
             cannabis-associated changes in sperm DNA methylation we
             found in human males who smoke cannabis (Murphy et al.,
             2018). In the current study we investigated the
             intergeneration effects of THC exposure of young adult male
             rats (0 or 2 mg/kg/day orally for 12 days) to the
             neurobehavioral development of their offspring. This
             paternal THC exposure was not found to significantly impact
             the clinical health of the offspring, including litter size,
             sex ratio, pup birth weight, survival and growth. However,
             it did cause a long-lasting significant impairment in
             attentional performance in the offspring relative to
             controls when they were tested in adulthood. There was also
             a significant increase in habituation of locomotor activity
             in the adult offspring of the males exposed to THC prior to
             mating. This study shows that premating paternal THC
             exposure even at a modest dose for a brief period can cause
             deleterious long-term behavioral effects in the offspring,
             notably significant impairment in an operant attention task.
             Further research should be conducted to determine the degree
             to which this type of risk is seen in humans and to
             investigate the mechanisms underlying these effects and
             possible treatments to ameliorate these long-term adverse
             behavioral consequences of paternal THC exposure.},
   Doi = {10.1016/j.ntt.2019.04.003},
   Key = {fds342565}
}

@article{fds341563,
   Author = {Rezvani, AH and Wells, C and Slade, S and Xiao, Y and Kellar, KJ and Levin,
             ED},
   Title = {Oral sazetidine-A, a selective α4β2* nicotinic receptor
             desensitizing agent, reduces nicotine self-administration in
             rats.},
   Journal = {Pharmacol Biochem Behav},
   Volume = {179},
   Pages = {109-112},
   Year = {2019},
   Month = {April},
   url = {http://dx.doi.org/10.1016/j.pbb.2019.02.007},
   Abstract = {Sazetidine-A selectively desensitizes α4β2 nicotinic
             receptors and also has partial agonist effects. We have
             shown that subcutaneous acute and repeated injections as
             well as chronic infusions of sazetidine-A significantly
             reduce intravenous (IV) nicotine self-administration in
             rats. To further investigate the promise of sazetidine-A as
             a smoking cessation aid, it is important to determine
             sazetidine-A effects with oral administration and the
             time-effect function for its action on nicotine
             self-administration. Young adult female Sprague-Dawley rats
             were trained to self-administer IV nicotine at the benchmark
             dose of 0.03 mg/kg/infusion dose in an operant FR1
             schedule in 45-min sessions. After five sessions of
             training, they were tested for the effects of acute oral
             doses of sazetidine-A (0, 0.3, 1 and 3 mg/kg) given
             30 min before testing. To determine the time-effect
             function, these rats were administered 0 or 3 mg/kg of
             sazetidine-A 1, 2, 4 or 23 h before the onset of testing.
             Our previous study showed that with subcutaneous injections,
             only 3 mg/kg of sazetidine-A significantly reduced
             nicotine self-administration, however, with oral
             administration of sazetidine-A lower dose of 1 mg/kg was
             also effective in reducing nicotine intake. A similar effect
             was seen in the time-effect study with 3 mg/kg of oral
             sazetidine-A causing a significant reduction in nicotine
             self-administration across all the time points of 1, 2, 4 or
             23 h after oral administration. These results advance the
             development of sazetidine-A as a possible aid for smoking
             cessation by showing effectiveness with oral administration
             and persistence of the effect over the course of a
             day.},
   Doi = {10.1016/j.pbb.2019.02.007},
   Key = {fds341563}
}

@article{fds342294,
   Author = {Slotkin, TA and Skavicus, S and Ko, A and Levin, ED and Seidler,
             FJ},
   Title = {Corrigendum to "The Developmental Neurotoxicity of Tobacco
             Smoke Can Be Mimicked by a Combination of Nicotine and
             Benzo[a]pyrene: Effects on Cholinergic and Serotonergic
             Systems".},
   Journal = {Toxicological Sciences},
   Volume = {168},
   Number = {1},
   Pages = {280},
   Year = {2019},
   Month = {March},
   url = {http://dx.doi.org/10.1093/toxsci/kfy304},
   Doi = {10.1093/toxsci/kfy304},
   Key = {fds342294}
}

@article{fds342295,
   Author = {Ideraabdullah, FY and Belenchia, AM and Rosenfeld, CS and Kullman,
             SW and Knuth, M and Mahapatra, D and Bereman, M and Levin, ED and Peterson,
             CA},
   Title = {Maternal vitamin D deficiency and developmental origins of
             health and disease (DOHaD).},
   Journal = {J Endocrinol},
   Year = {2019},
   Month = {March},
   url = {http://dx.doi.org/10.1530/JOE-18-0541},
   Abstract = {Vitamin D is an essential nutrient that is metabolized in
             the body to generate an active metabolite (1,25(OH)2D) with
             hormone-like activity and highly diverse roles in cellular
             function. Vitamin D deficiency (VDD) is a prevalent but
             easily preventable nutritional disturbance. Emerging
             evidence demonstrates the importance of sufficient vitamin D
             concentrations during fetal life with deficiencies leading
             to long-term effects into adulthood. Here, we provide a
             detailed review and perspective of evidence for the role of
             maternal VDD in offspring long term health, particularly as
             it relates to Developmental Origins of Health and Disease
             (DOHaD). We focus on roles in neurobehavioral and
             cardiometabolic disorders in humans and highlight recent
             findings from zebrafish and rodent models that probe
             potential mechanisms linking early life VDD to later life
             health outcomes. Moreover, we explore evidence implicating
             epigenetic mechanisms as a mediator of this link. Gaps in
             our current understanding of how maternal VDD might result
             in deleterious offspring outcomes later in life are also
             addressed.},
   Doi = {10.1530/JOE-18-0541},
   Key = {fds342295}
}

@article{fds340154,
   Author = {Levin, ED and Rezvani, AH and Wells, C and Slade, S and Yenugonda, VM and Liu, Y and Brown, ML and Xiao, Y and Kellar, KJ},
   Title = {α4β2 Nicotinic receptor desensitizing compounds can
             decrease self-administration of cocaine and methamphetamine
             in rats.},
   Journal = {Eur J Pharmacol},
   Volume = {845},
   Pages = {1-7},
   Year = {2019},
   Month = {February},
   url = {http://dx.doi.org/10.1016/j.ejphar.2018.12.010},
   Abstract = {Sazetidine-A [6-(5(((S)-azetidine-2-yl)methoxy)pyridine-3-yl)hex-5-yn-1-ol]
             is a selective α4β2 nicotinic receptor desensitizing agent
             and partial agonist. Sazetidine-A has been shown in our
             previous studies to significantly reduce nicotine and
             alcohol self-administration in rats. The question arises
             whether sazetidine-A would reduce self-administration of
             other addictive drugs as well. Nicotinic receptors on the
             dopaminergic neurons in the ventral tegmental area play an
             important role in controlling the activity of these neurons
             and release of dopamine in the nucleus accumbens, which is
             critical mechanism for reinforcing value of drugs of abuse.
             Previously, we showed that the nonspecific nicotinic
             antagonist mecamylamine significantly reduces cocaine
             self-administration in rats. In this study, we acutely
             administered systemically sazetidine-A and two other
             selective α4β2 nicotinic receptor-desensitizing agents,
             VMY-2-95 and YL-2-203, to young adult female Sprague-Dawley
             rats and determined their effects on IV self-administration
             of cocaine and methamphetamine. Cocaine self-administration
             was significantly reduced by 0.3 mg/kg of sazetidine-A. In
             another set of rats, sazetidine-A (3 mg/kg) significantly
             reduced methamphetamine self-administration. VMY-2-95
             significantly reduced both cocaine and methamphetamine
             self-administration with threshold effective doses of 3 and
             0.3 mg/kg, respectively. In contrast, YL-2-203 did not
             significantly reduce cocaine self-administration at the same
             dose range and actually significantly increased cocaine
             self-administration at the 1 mg/kg dose. YL-2-203
             (3 mg/kg) did significantly decrease methamphetamine
             self-administration. Sazetidine-A and VMY-2-95 are promising
             candidates to develop as new treatments to help addicts
             successfully overcome a variety of addictions including
             tobacco, alcohol as well as the stimulant drugs cocaine and
             methamphetamine.},
   Doi = {10.1016/j.ejphar.2018.12.010},
   Key = {fds340154}
}

@article{fds337701,
   Author = {Oliveri, AN and Levin, ED},
   Title = {Dopamine D1 and D2 receptor antagonism during development
             alters later behavior in zebrafish.},
   Journal = {Behav Brain Res},
   Volume = {356},
   Pages = {250-256},
   Year = {2019},
   Month = {January},
   url = {http://dx.doi.org/10.1016/j.bbr.2018.08.028},
   Abstract = {This study sought to examine the long-term behavioral
             impacts of dopamine D1 and D2 receptor antagonism during
             development in zebrafish (Danio rerio). Zebrafish embryos of
             both the AB* and 5D strains were exposed via immersion to
             either the D1 receptor antagonist SCH-23,390 or the D2
             receptor antagonist haloperidol, at either 0.5 or 1.5-μM,
             from 5 h post-fertilization to 5 days post-fertilization.
             Aquarium water served as a control. Fish were then either
             tested as larvae on day 6 post-fertilization on a light/dark
             locomotor assay, or were grown to adulthood and tested on a
             behavioral battery that included assays for novel
             environment exploration, startle habituation, social
             affiliation, and predator escape (AB* strain only). Overall,
             developmental exposure to dopamine D1 and D2 receptor
             antagonists caused clear effects in larval locomotor
             behavior, driving hyperactivity in dark phases and
             hypoactivity in light phases. Additionally, control fish
             from the two strains were significantly different from each
             other (p < 0.05) with the AB* fish being more active
             than SD during the dark periods of the test. In the adult
             behavioral battery, developmental exposure to 1.5-μM of the
             D1 antagonist SCH-23390 significantly reduced activity
             (p < 0.05) in the predator escape assay. Despite the
             fact that embryonic exposure to D1 and D2 receptor
             antagonists caused clear behavioral alterations in larval
             activity there were much more subtle effects persisting into
             adulthood.},
   Doi = {10.1016/j.bbr.2018.08.028},
   Key = {fds337701}
}

@article{fds339670,
   Author = {DiPalma, D and Rezvani, AH and Willette, B and Wells, C and Slade, S and Hall, BJ and Levin, ED},
   Title = {Persistent attenuation of nicotine self-administration in
             rats by co-administration of chronic nicotine infusion with
             the dopamine D1 receptor antagonist SCH-23390 or the
             serotonin 5-HT2C agonist lorcaserin.},
   Journal = {Pharmacol Biochem Behav},
   Volume = {176},
   Pages = {16-22},
   Year = {2019},
   Month = {January},
   url = {http://dx.doi.org/10.1016/j.pbb.2018.11.002},
   Abstract = {Tobacco addiction each year causes millions of deaths
             worldwide. Brain nicotinic acetylcholine receptors have been
             shown to be central to tobacco addiction. Nicotine
             replacement therapy aids tobacco cessation, but the success
             rate is still far too low. This may in part be due to the
             fact that neurons with nicotinic receptors are not the only
             neural systems involved in tobacco addiction. Interacting
             neural systems also play important roles in tobacco
             addiction. Nicotine increases the release of a variety of
             neurotransmitters, including dopamine and serotonin.
             Dopamine, in particular dopamine D1 receptors, has been
             shown to be involved in the reinforcing action of nicotine.
             Serotonin through its actions on 5-HT2C receptors has been
             shown to play a key role in modulating the reinforcement of
             addictive drugs, including nicotine and alcohol. Combination
             of treatments could provide greater treatment efficacy.
             These studies were conducted to evaluate combination
             therapies utilizing nicotine replacement therapy in
             conjunction with either a dopamine D1 receptor antagonist
             SCH-23390 or a serotonin 5-HT2C receptor agonist,
             lorcaserin. Female Sprague-Dawley rats were given access to
             self-administer nicotine via IV infusions. Osmotic pumps
             were implanted to reproduce the kinetic of chronic nicotine
             patch therapy. SCH-23390 (0.02 mg/kg) or lorcaserin
             (0.6 mg/kg) were administered prior to nicotine
             self-administration sessions. Reproducing earlier findings
             SCH-23390, lorcaserin and nicotine replacement therapy were
             effective at reducing IV nicotine self-administration. 5HT2C
             agonist treatment had additive effects with chronic nicotine
             infusion for significantly lowering nicotine
             self-administration. This study demonstrates the feasibility
             of combination of chronic nicotine with therapies targeting
             non-nicotinic receptors as treatment options for tobacco
             addiction.},
   Doi = {10.1016/j.pbb.2018.11.002},
   Key = {fds339670}
}

@article{fds336089,
   Author = {Pitt, JA and Trevisan, R and Massarsky, A and Kozal, JS and Levin, ED and Di Giulio and RT},
   Title = {Maternal transfer of nanoplastics to offspring in zebrafish
             (Danio rerio): A case study with nanopolystyrene.},
   Journal = {The Science of the Total Environment},
   Volume = {643},
   Pages = {324-334},
   Year = {2018},
   Month = {December},
   url = {http://dx.doi.org/10.1016/j.scitotenv.2018.06.186},
   Abstract = {Plastics are ubiquitous anthropogenic contaminants that are
             a growing concern in aquatic environments. The ecological
             implications of macroplastics pollution are well documented,
             but less is known about nanoplastics. The current study
             investigates the potential adverse effects of nanoplastics,
             which likely contribute to the ecological burden of plastic
             pollution. To this end, we examined whether a dietary
             exposure of adult zebrafish (Danio rerio) to polystyrene
             nanoparticles (PS NPs) could lead to the transfer of
             nanoplastics to the offspring, and whether nanoplastics
             exposure affects zebrafish physiology. Specifically, adult
             female and male zebrafish (F0 generation) were exposed to PS
             NPs via diet for one week and bred to produce the F1
             generation. Four F1 groups were generated: control
             (unexposed females and males), maternal (exposed females),
             paternal (exposed males), and co-parental (exposed males and
             females). Co-parental PS NP exposure did not significantly
             affect reproductive success. Assessment of tissues from F0
             fish revealed that exposure to PS NPs significantly reduced
             glutathione reductase activity in brain, muscle, and testes,
             but did not affect mitochondrial function parameters in
             heart or gonads. Assessment of F1 embryos and larvae
             revealed that PS NPs were present in the yolk sac,
             gastrointestinal tract, liver, and pancreas of the
             maternally and co-parentally exposed F1 embryos/larvae.
             Bradycardia was also observed in embryos from maternal and
             co-parental exposure groups. In addition, the activity of
             glutathione reductase and the levels of thiols were reduced
             in F1 embryos/larvae from maternal and/or co-parental
             exposure groups. Mitochondrial function and locomotor
             activity were not affected in F1 larvae. This study
             demonstrates that (i) PS NPs are transferred from mothers to
             offspring, and (ii) exposure to PS NPs modifies the
             antioxidant system in adult tissues and F1 larvae. We
             conclude that PS NPs could bioaccumulate and be passed on to
             the offspring, but this does not lead to major physiological
             disturbances.},
   Doi = {10.1016/j.scitotenv.2018.06.186},
   Key = {fds336089}
}

@article{fds336088,
   Author = {Cauley, M and Hall, BJ and Abreu-Villaça, Y and Junaid, S and White, H and Kiany, A and Slotkin, TA and Levin, ED},
   Title = {Critical developmental periods for effects of low-level
             tobacco smoke exposure on behavioral performance.},
   Journal = {Neurotoxicology},
   Volume = {68},
   Pages = {81-87},
   Year = {2018},
   Month = {September},
   url = {http://dx.doi.org/10.1016/j.neuro.2018.07.012},
   Abstract = {Tobacco exposure during development leads to neurobehavioral
             dysfunction in children, even when exposure is limited to
             secondhand smoke. We have previously shown in rats that
             developmental exposure to tobacco smoke extract (TSE), at
             levels mimicking secondhand smoke, starting preconception
             and extending throughout gestation, evoked subsequent
             locomotor hyperactivity and cognitive impairment. These
             effects were greater than those caused by equivalent
             exposures to nicotine alone, implying that other agents in
             tobacco smoke contributed to the adverse behavioral effects.
             In the present study, we examined the critical developmental
             windows of vulnerability for these effects, restricting TSE
             administration (0.2 mg/kg/day nicotine equivalent, or DMSO
             vehicle, delivered by subcutaneously-implanted pumps) to
             three distinct 10 day periods: the 10 days preceding mating,
             the first 10 days of gestation (early gestation), or the
             second 10 days of gestation (late gestation). The principal
             behavioral effects revealed a critical developmental window
             of vulnerability, as well as sex selectivity. Late
             gestational TSE exposure significantly increased errors in
             the initial training on the radial-arm maze in female
             offspring, whereas no effects were seen in males exposed
             during late gestation, or with either sex in the other
             exposure windows. In attentional testing with the visual
             signal detection test, male offspring exposed to TSE during
             early or late gestation showed hypervigilance during
             low-motivating conditions. These results demonstrate that
             gestational TSE exposure causes persistent behavioral
             effects that are dependent on the developmental window in
             which exposure occurs. The fact that effects were seen at
             TSE levels modeling secondhand smoke, emphasizes the need
             for decreasing involuntary tobacco smoke exposure,
             particularly during pregnancy.},
   Doi = {10.1016/j.neuro.2018.07.012},
   Key = {fds336088}
}

@article{fds329144,
   Author = {Glazer, L and Wells, CN and Drastal, M and Odamah, K-A and Galat, RE and Behl, M and Levin, ED},
   Title = {Developmental exposure to low concentrations of two
             brominated flame retardants, BDE-47 and BDE-99, causes
             life-long behavioral alterations in zebrafish.},
   Journal = {Neurotoxicology},
   Volume = {66},
   Pages = {221-232},
   Year = {2018},
   Month = {May},
   url = {http://dx.doi.org/10.1016/j.neuro.2017.09.007},
   Abstract = {BACKGROUND: Polybrominated diphenyl ethers (PBDEs) were
             widely used as flame retardants until the early 2000s,
             mainly in home furnishings and electronics. The persistence
             of PBDEs in the environment leads to continued ubiquitous
             exposure to low levels, with infants and children
             experiencing higher exposures than adults. Accumulating
             evidence suggest that low-level exposures during early life
             stages can affect brain development and lead to long-term
             behavioral impairments. We investigated the effects of
             zebrafish exposure to low doses of the two prominent PBDEs;
             2,2',4,4',5,-Pentabromodiphenyl ether (BDE-99) and
             2,2',4,4',-Tetrabromodiphenyl ether (BDE-47), during
             embryo-development on short- and long-term behavioral
             endpoints. We included the organophosphate pesticide
             chlorpyrifos (CPF) due to its well documented neurotoxicity
             across species from zebrafish to humans. METHODS: Zebrafish
             embryos were exposed to the following individual treatments;
             0.1% DMSO (vehicle control); 0.3μM CPF; 0.01, 0.03, 0.1,
             0.3μM BDE-47; 0.003, 0.03, 0.3, 1, 3, 10, 20μM BDE-99 from
             5 until 120h post fertilization (hpf). Low exposure levels
             were determined as those not causing immediate overt
             toxicity, and behavior assays were conducted in the
             low-level range. At 144 hpf the larvae were tested for
             locomotor activity. At approximately 6 months of age adult
             zebrafish were tested in a behavioral battery including
             assays for anxiety-related behavior, sensorimotor response
             and habituation, social interaction, and predator avoidance.
             RESULTS: In the short-term, larval locomotor activity was
             reduced in larvae treated with 0.3μM CPF and 0.1μM BDE-47.
             BDE-99 treatment caused non-monotonic dose effects, with
             0.3μM causing hyperactivity and 1μM or higher causing
             hypoactivity. In the long-term, adult anxiety-related
             behavior was reduced in all treatments as measured in both
             the novel tank dive test and tap test. DISCUSSION: We show
             that exposure of zebrafish embryos to low concentrations of
             the brominated flame retardants BDE-47 and BDE-99, and the
             organophosphate pesticide CPF, caused both short- and
             long-term behavioral impairments. Interestingly, we also
             found that at very low exposure concentrations, where there
             were no visible effects on larval activity, adult behavior
             was still strongly affected.},
   Doi = {10.1016/j.neuro.2017.09.007},
   Key = {fds329144}
}

@article{fds333553,
   Author = {Oliveri, AN and Ortiz, E and Levin, ED},
   Title = {Developmental exposure to an organophosphate flame retardant
             alters later behavioral responses to dopamine antagonism in
             zebrafish larvae.},
   Journal = {Neurotoxicol Teratol},
   Volume = {67},
   Pages = {25-30},
   Year = {2018},
   Month = {May},
   url = {http://dx.doi.org/10.1016/j.ntt.2018.03.002},
   Abstract = {Human exposure to organophosphate flame retardants (OPFRs)
             is widespread, including pregnant women and young children
             with whom developmental neurotoxic risk is a concern. Given
             similarities of OPFRs to organophosphate (OP) pesticides,
             research into the possible neurotoxic impacts of
             developmental OPFR exposure has been growing. Building upon
             research implicating exposure to OP pesticides in
             dopaminergic (DA) dysfunction, we exposed developing
             zebrafish to the OPFR tris(1,3-dichloroisopropyl) phosphate
             (TDCIPP), during the first 5 days following fertilization.
             On day 6, larvae were challenged with acute administration
             of dopamine D1 and D2 receptor antagonists and then tested
             in a light-dark locomotor assay. We found that both
             developmental TDCIPP exposure and acute dopamine D1 and D2
             antagonism decreased locomotor activity separately. The OPFR
             and DA effects were not additive; rather, TDCIPP blunted
             further D1 and D2 antagonist-induced decreases in activity.
             Our results suggest that TDCIPP exposure may be disrupting
             dopamine signaling. These findings support further research
             on the effects of OPFR exposure on the normal
             neurodevelopment of DA systems, whether these results might
             persist into adulthood, and whether they interact with OPFR
             effects on other neurotransmitter systems in producing the
             developmental neurobehavioral toxicity.},
   Doi = {10.1016/j.ntt.2018.03.002},
   Key = {fds333553}
}

@article{fds332068,
   Author = {Rezvani, AH and Tizabi, Y and Slade, S and Getachew, B and Levin,
             ED},
   Title = {Sub-anesthetic doses of ketamine attenuate nicotine
             self-administration in rats.},
   Journal = {Neurosci Lett},
   Volume = {668},
   Pages = {98-102},
   Year = {2018},
   Month = {March},
   url = {http://dx.doi.org/10.1016/j.neulet.2018.01.022},
   Abstract = {Smoking cessation strategies are of prime medical
             importance. Despite availability of various pharmacological
             agents in combating addiction to nicotine, more effective
             medications are needed. Based on recent findings, the
             glutamatergic system in the brain may provide novel targets.
             Here, we evaluated the effects of acute administration of
             sub-anesthetic doses of ketamine, an NMDA receptor
             antagonist, in both male and female Sprague-Dawley rats
             trained to self-administer nicotine. Animals were injected
             subcutaneously with 5, 7.5 and 10 mg/kg ketamine or saline
             and the effects on the number of intravenous nicotine
             infusions during a 45 min session was measured. Ketamine
             treatment significantly reduced nicotine self-administration
             in a dose-dependent manner. Moreover, a differential
             sensitivity between the sexes was observed as male rats
             responded to a lower dose of ketamine and with higher
             magnitude of effect than female rats. It is concluded that
             glutamatergic receptor manipulations may offer a novel and
             potentially sex-dependent intervention in nicotine
             addiction.},
   Doi = {10.1016/j.neulet.2018.01.022},
   Key = {fds332068}
}

@article{fds332218,
   Author = {Levin, ED and Wells, C and Slade, S and Rezvani, AH},
   Title = {Mutually augmenting interactions of dextromethorphan and
             sazetidine-A for reducing nicotine self-administration in
             rats.},
   Journal = {Pharmacol Biochem Behav},
   Volume = {166},
   Pages = {42-47},
   Year = {2018},
   Month = {March},
   url = {http://dx.doi.org/10.1016/j.pbb.2018.01.005},
   Abstract = {A variety of nicotinic drug treatments have been found to
             decrease nicotine self-administration. However, interactions
             of drugs affecting different nicotinic receptor subtypes
             have not been much investigated. This study investigated the
             interactions between dextromethorphan, which blocks
             nicotinic α3β2 receptors as well as a variety of other
             receptors with sazetidine-A which is a potent and selective
             α4β2 nicotinic receptor partial agonist with desensitizing
             properties. This interaction was compared with
             dextromethorphan combination treatment with mecamylamine,
             which is a nonspecific nicotinic channel blocker.
             Co-administration of dextromethorphan (either 0.5 or
             5 mg/kg) and lower dose of sazetidine-A (0.3 mg/kg)
             caused a significant reduction in nicotine SA. With regard
             to food-motivated responding, 3 mg/kg of sazetidine-A
             given alone caused a significant decrease in food intake.
             However, the lower 0.3 mg/kg sazetidine-A dose did not
             significantly affect food-motivated responding even when
             given in combination with the higher 5 mg/kg
             dextromethorphan dose which itself caused a significant
             decrease in food motivated responding. Interestingly, this
             higher dextromethorphan dose significantly attenuated the
             decrease in food motivated responding caused by 3 mg/kg of
             sazetidine-A. Locomotor activity was increased by the lower
             0.3 mg/kg sazetidine-A dose and decreased by the 5 mg/kg
             dextromethorphan dose. Mecamylamine at the doses (0.1 and
             1 mg/kg) did not affect nicotine SA, but at 1 mg/kg
             significantly decreased food-motivated responding. None of
             the mecamylamine doses augmented the effect of
             dextromethorphan in reducing nicotine self-administration.
             These studies showed that the combination of
             dextromethorphan and sazetidine-A had mutually potentiating
             effects, which could provide a better efficacy for promoting
             smoking cessation, however the strength of the interactions
             was fairly modest.},
   Doi = {10.1016/j.pbb.2018.01.005},
   Key = {fds332218}
}

@article{fds333002,
   Author = {Massarsky, A and Abdel, A and Glazer, L and Levin, ED and Di Giulio,
             RT},
   Title = {Neurobehavioral effects of 1,2-propanediol in zebrafish
             (Danio rerio).},
   Journal = {Neurotoxicology},
   Volume = {65},
   Pages = {111-124},
   Year = {2018},
   Month = {March},
   url = {http://dx.doi.org/10.1016/j.neuro.2018.02.007},
   Abstract = {The use of electronic cigarettes (e-cigarettes) is
             increasing despite insufficient information concerning their
             long-term effects, including the effects of maternal
             e-cigarette use on pre- and postnatal development. Our
             previous study demonstrated that developmental exposure to
             1,2-propanediol (a principal component of e-cigarette
             liquid) affected early development of zebrafish, causing
             reduced growth, deformities, and hyperactive swimming
             behavior in larvae. The current study extends assessment of
             the developmental toxicity of 1,2-propanediol by examining
             additional long-term behavioral effects. We demonstrate that
             embryonic/larval exposure of zebrafish to 1,2-propanediol
             (0.625% or 1.25%) not only affected behavioral parameters in
             the larvae, but also caused persisting behavioral effects in
             adults after early developmental exposure. Additional
             parameters, including neural and vascular development in
             larvae, stress response in adults, and concentration of
             neurotransmitters dopamine and serotonin in adult brain were
             examined, in order to explain the behavioral differences.
             These additional assessments did not find 1,2-propanediol
             exposure to significantly affect Tg(Neurog1:GFP) or the
             transcript abundance of neural genes (Neurog1, Ascl1a,
             Elavl3, and Lef1). Vascular development was not found to be
             affected by 1,2-propanediol exposure, as inferred from
             experiments with Tg(Flk1:eGFP) zebrafish; however,
             transcript abundance of vascular genes (Flk1, Vegf, Tie-2,
             and Angpt1) was decreased. No statistically significant
             changes were noted for plasma cortisol or brain
             neurotransmitters in adult fish. Lastly, analysis of gene
             transcripts involved with 1,2-propanediol metabolism (Adh5,
             Aldh2.1, and Ldha) showed an increase in Adh5 transcript.
             This is the first study to demonstrate that developmental
             exposure to 1,2-propanediol has long-term neurobehavioral
             consequences in adult zebrafish, showing that e-cigarettes
             contain substances potentially harmful to
             neurodevelopment.},
   Doi = {10.1016/j.neuro.2018.02.007},
   Key = {fds333002}
}

@article{fds332917,
   Author = {Pitt, JA and Kozal, JS and Jayasundara, N and Massarsky, A and Trevisan,
             R and Geitner, N and Wiesner, M and Levin, ED and Di Giulio,
             RT},
   Title = {Uptake, tissue distribution, and toxicity of polystyrene
             nanoparticles in developing zebrafish (Danio
             rerio).},
   Journal = {Aquat Toxicol},
   Volume = {194},
   Pages = {185-194},
   Year = {2018},
   Month = {January},
   url = {http://dx.doi.org/10.1016/j.aquatox.2017.11.017},
   Abstract = {Plastic pollution is a critical environmental concern and
             comprises the majority of anthropogenic debris in the ocean,
             including macro, micro, and likely nanoscale (less than
             100nm in at least one dimension) plastic particles. While
             the toxicity of macroplastics and microplastics is
             relatively well studied, the toxicity of nanoplastics is
             largely uncharacterized. Here, fluorescent polystyrene
             nanoparticles (PS NPs) were used to investigate the
             potential toxicity of nanoplastics in developing zebrafish
             (Danio rerio), as well as to characterize the uptake and
             distribution of the particles within embryos and larvae.
             Zebrafish embryos at 6h post-fertilization (hpf) were
             exposed to PS NPs (0.1, 1, or 10ppm) until 120 hpf. Our
             results demonstrate that PS NPs accumulated in the yolk sac
             as early as 24 hpf and migrated to the gastrointestinal
             tract, gallbladder, liver, pancreas, heart, and brain
             throughout development (48-120 hpf). Accumulation of PS NPs
             decreased during the depuration phase (120-168 hpf) in all
             organs, but at a slower rate in the pancreas and
             gastrointestinal tract. Notably, exposure to PS NPs did not
             induce significant mortality, deformities, or changes to
             mitochondrial bioenergetics, but did decrease the heart
             rate. Lastly, exposure to PS NPs altered larval behavior as
             evidenced by swimming hypoactivity in exposed larvae. Taken
             together, these data suggest that at least some nanoplastics
             can penetrate the chorion of developing zebrafish,
             accumulate in the tissues, and affect physiology and
             behavior, potentially affecting organismal fitness in
             contaminated aquatic ecosystems.},
   Doi = {10.1016/j.aquatox.2017.11.017},
   Key = {fds332917}
}

@article{fds330580,
   Author = {Lacagnina, MJ and Kopec, AM and Cox, SS and Hanamsagar, R and Wells, C and Slade, S and Grace, PM and Watkins, LR and Levin, ED and Bilbo,
             SD},
   Title = {Opioid Self-Administration is Attenuated by Early-Life
             Experience and Gene Therapy for Anti-Inflammatory IL-10 in
             the Nucleus Accumbens of Male Rats.},
   Journal = {Neuropsychopharmacology},
   Volume = {42},
   Number = {11},
   Pages = {2128-2140},
   Year = {2017},
   Month = {October},
   url = {http://dx.doi.org/10.1038/npp.2017.82},
   Abstract = {Early-life conditions can contribute to the propensity for
             developing neuropsychiatric disease, including substance
             abuse disorders. However, the long-lasting mechanisms that
             shape risk or resilience for drug addiction remain unclear.
             Previous work has shown that a neonatal handling procedure
             in rats (which promotes enriched maternal care) attenuates
             morphine conditioning, reduces morphine-induced glial
             activation, and increases microglial expression of the
             anti-inflammatory cytokine interleukin-10 (IL-10). We thus
             hypothesized that anti-inflammatory signaling may underlie
             the effects of early-life experience on later-life opioid
             drug-taking. Here we demonstrate that neonatal handling
             attenuates intravenous self-administration of the opioid
             remifentanil in a drug-concentration-dependent manner.
             Transcriptional profiling of the nucleus accumbens (NAc)
             from handled rats following repeated exposure to
             remifentanil reveals a suppression of pro-inflammatory
             cytokine and chemokine gene expression, consistent with an
             anti-inflammatory phenotype. To determine if
             anti-inflammatory signaling alters drug-taking behavior, we
             administered intracranial injections of plasmid DNA encoding
             IL-10 (pDNA-IL-10) into the NAc of non-handled rats. We
             discovered that pDNA-IL-10 treatment reduces remifentanil
             self-administration in a drug-concentration-dependent
             manner, similar to the effect of handling. In contrast,
             neither handling nor pDNA-IL-10 treatment alters
             self-administration of food or sucrose rewards. These
             collective observations suggest that neuroimmune signaling
             mechanisms in the NAc are shaped by early-life experience
             and may modify motivated behaviors for opioid drugs.
             Moreover, manipulation of the IL-10 signaling pathway
             represents a novel approach for influencing opioid
             reinforcement.},
   Doi = {10.1038/npp.2017.82},
   Key = {fds330580}
}

@article{fds327308,
   Author = {Rezvani, AH and Slade, S and Wells, C and Yenugonda, VM and Liu, Y and Brown, ML and Xiao, Y and Kellar, KJ and Levin, ED},
   Title = {Differential efficacies of the nicotinic α4β2
             desensitizing agents in reducing nicotine
             self-administration in female rats.},
   Journal = {Psychopharmacology (Berl)},
   Volume = {234},
   Number = {17},
   Pages = {2517-2523},
   Year = {2017},
   Month = {September},
   url = {http://dx.doi.org/10.1007/s00213-017-4641-6},
   Abstract = {RATIONALE AND OBJECTIVES: Desensitization of neuronal
             nicotinic acetylcholine receptors holds promise as an
             effective treatment of tobacco addiction. Previously, we
             found that sazetidine-A (Saz-A), which selectively
             desensitizes α4β2 nicotinic receptors, significantly
             decreased intravenous (IV) nicotine self-administration (SA)
             in rats with an effective dose of 3 mg/kg in acute and
             repeated injection studies. We also found that chronic
             infusions of Saz-A at doses of 2 and 6 mg/kg/day
             significantly reduced nicotine SA in rats. In continuing
             studies, we have characterized other Saz-A analogs, YL-2-203
             and VMY-2-95, to determine their efficacies in reducing
             nicotine SA in rats. METHODS: Young adult female
             Sprague-Dawley rats were fitted with IV catheters and were
             trained for nicotine SA (0.03 mg/kg/infusion) on a fixed
             ratio 1 schedule for ten sessions. The same rats were also
             implanted subcutaneously with osmotic minipumps to
             continually deliver 2 or 6 mg/kg body weight YL-2-203,
             VMY-2-95, or saline for four consecutive weeks. RESULTS:
             Chronic administration of VMY-2-95 at doses of 2 and
             6 mg/kg/day caused significant (p < 0.01) decreases in
             nicotine SA over the 2 weeks of continued nicotine SA and
             for the 1-week period of resumed access after a week of
             enforced abstinence, whereas chronic administration of
             YL-2-203 at the same doses was not found to be effective.
             CONCLUSIONS: These studies, together with our previous
             studies of Saz-A, revealed a spectrum of efficacies for
             these α4β2 nicotinic receptor desensitizing agents and
             provide a path forward for the most effective compounds to
             be further developed as possible aids to smoking
             cessation.},
   Doi = {10.1007/s00213-017-4641-6},
   Key = {fds327308}
}

@article{fds330581,
   Author = {Massarsky, A and Abdel, A and Glazer, L and Levin, ED and Di Giulio,
             RT},
   Title = {Exposure to 1,2-Propanediol Impacts Early Development of
             Zebrafish (Danio rerio) and Induces Hyperactivity.},
   Journal = {Zebrafish},
   Volume = {14},
   Number = {3},
   Pages = {216-222},
   Year = {2017},
   Month = {June},
   url = {http://dx.doi.org/10.1089/zeb.2016.1400},
   Abstract = {The use of electronic cigarettes (e-cigarettes) is
             increasing as an alternative to tobacco burning cigarettes;
             however, their safety remains to be fully determined. The
             long-term effects of e-cigarettes are unknown, including the
             effects of maternal e-cigarette use on pre- and postnatal
             development. Additional research on the safety of
             e-cigarettes is needed. Especially useful would be
             information from high- and moderate-throughput economic
             model systems. This study investigates the effects of
             1,2-propanediol, which was identified as the main component
             of e-cigarette liquid, on early development of zebrafish (an
             in vivo high-throughput model system that was recently
             proposed for the study of tobacco cigarette and e-cigarette
             toxicity). Zebrafish embryos were exposed to 1.25% or 2.5%
             1,2-propanediol from 6 to 72 h post-fertilization (hpf).
             We show that exposure to 1,2-propanediol did not
             significantly affect mortality. Hatching success was
             significantly lower in 2.5% 1,2-propanediol-exposed embryos
             at 48 hpf, but at 72 hpf no significant differences were
             noted. Moreover, exposure to 1,2-propanediol reduced growth
             and increased the incidence of string heart, pericardial
             edema, and yolk sac edema. Most importantly, developmental
             exposure to 1.25% 1,2-propanediol caused hyperactive
             swimming behavior in larvae. This study demonstrates that
             1,2-propanediol has adverse impacts on early development in
             zebrafish.},
   Doi = {10.1089/zeb.2016.1400},
   Key = {fds330581}
}

@article{fds324065,
   Author = {Hall, BJ and Abreu-Villaça, Y and Cauley, M and Junaid, S and White, H and Kiany, A and Levin, ED},
   Title = {The ventral hippocampal muscarinic cholinergic system plays
             a key role in sexual dimorphisms of spatial working memory
             in rats.},
   Journal = {Neuropharmacology},
   Volume = {117},
   Pages = {106-113},
   Year = {2017},
   Month = {May},
   url = {http://dx.doi.org/10.1016/j.neuropharm.2017.01.019},
   Abstract = {Sex differences in cognitive processing and function have
             been documented in human and animal studies. Females have
             been found to perform better than males on non-spatial
             memory tasks, while males tend to outperform females on
             spatial memory tasks. The neural mechanisms underlying these
             sexual dimorphisms are unclear. However, it is known that
             the cholinergic system is critically involved in memory
             processes, and there are notable differences between males
             and females in cholinergic system function and receptor
             expression. In particular, there are sex differences in the
             processing of information in the frontal cortex and
             hippocampus. In this study, we examined the roles of
             muscarinic and nicotinic acetylcholine receptors in the
             medial frontal cortex (MfC) and ventral hippocampus (VH) on
             spatial working memory in male and female rats. Local
             infusions of scopolamine (SCOP) and mecamylamine (MEC) (10,
             20, 50 μg/side) were used to antagonize these receptors in
             each respective brain region during performance in the
             16-arm radial arm maze. Infusions of SCOP into the VH caused
             a significant increase in memory errors in female rats, but
             had no significant effect on males, while infusions of MEC
             into the VH had no effect on either sex. Infusions of both
             SCOP (50 μg/side) and MEC (20 μg/side) into the MfC caused
             working memory impairments in both sexes. These results show
             that muscarinic acetylcholine receptors in the VH are
             differentially vulnerable to spatial memory impairments in
             females. Ventral hippocampal muscarinic acetylcholine
             receptors may play a key role in male-female differences in
             spatial memory.},
   Doi = {10.1016/j.neuropharm.2017.01.019},
   Key = {fds324065}
}

@article{fds330582,
   Author = {van Thriel, C and Levin, E and Lein, P and Costa, LG and Westerink,
             RHS},
   Title = {Neural mechanisms of functional impairment across the
             lifespan: The 15th Biennial Meeting of the International
             Neurotoxicology Association and 39th Annual Meeting of the
             Neurobehavioral Teratology Society.},
   Journal = {Neurotoxicology},
   Volume = {59},
   Pages = {131-132},
   Year = {2017},
   Month = {March},
   url = {http://dx.doi.org/10.1016/j.neuro.2017.03.003},
   Doi = {10.1016/j.neuro.2017.03.003},
   Key = {fds330582}
}

@article{fds324066,
   Author = {Abreu-Villaça, Y and Levin, ED},
   Title = {Developmental neurotoxicity of succeeding generations of
             insecticides.},
   Journal = {Environ Int},
   Volume = {99},
   Pages = {55-77},
   Year = {2017},
   Month = {February},
   url = {http://dx.doi.org/10.1016/j.envint.2016.11.019},
   Abstract = {Insecticides are by design toxic. They must be toxic to
             effectively kill target species of insects. Unfortunately,
             they also have off-target toxic effects that can harm other
             species, including humans. Developmental neurotoxicity is
             one of the most prominent off-target toxic risks of
             insecticides. Over the past seven decades several classes of
             insecticides have been developed, each with their own
             mechanisms of effect and toxic side effects. This review
             covers the developmental neurotoxicity of the succeeding
             generations of insecticides including organochlorines,
             organophosphates, pyrethroids, carbamates and
             neonicotinoids. The goal of new insecticide development is
             to more effectively kill target species with fewer toxic
             side effects on non-target species. From the experience with
             the developmental neurotoxicity caused by the generations of
             insecticides developed in the past advice is offered how to
             proceed with future insecticide development to decrease
             neurotoxic risk.},
   Doi = {10.1016/j.envint.2016.11.019},
   Key = {fds324066}
}

@article{fds330184,
   Author = {Macaulay, LJ and Chernick, M and Chen, A and Hinton, DE and Bailey, JM and Kullman, SW and Levin, ED and Stapleton, HM},
   Title = {Exposure to a PBDE/OH-BDE mixture alters juvenile zebrafish
             (Danio rerio) development.},
   Journal = {Environ Toxicol Chem},
   Volume = {36},
   Number = {1},
   Pages = {36-48},
   Year = {2017},
   Month = {January},
   url = {http://dx.doi.org/10.1002/etc.3535},
   Abstract = {Polybrominated diphenyl ethers (PBDEs) and their metabolites
             (e.g., hydroxylated BDEs [OH-BDEs]) are contaminants
             frequently detected together in human tissues and are
             structurally similar to thyroid hormones. Thyroid hormones
             partially mediate metamorphic transitions between life
             stages in zebrafish, making this a critical developmental
             window that may be vulnerable to chemicals disrupting
             thyroid signaling. In the present study, zebrafish were
             exposed to 6-OH-BDE-47 (30 nM; 15 μg/L) alone, or to a
             low-dose (30 μg/L) or high-dose (600 μg/L) mixture of
             PentaBDEs, 6-OH-BDE-47 (0.5-6 μg/L), and
             2,4,6-tribromophenol (5-100 μg/L) during juvenile
             development (9-23 d postfertilization) and evaluated for
             developmental endpoints mediated by thyroid hormone
             signaling. Fish were sampled at 3 time points and examined
             for developmental and skeletal morphology, apical thyroid
             and skeletal gene markers, and modifications in swimming
             behavior (as adults). Exposure to the high-dose mixture
             resulted in >85% mortality within 1 wk of exposure,
             despite being below reported acute toxicity thresholds for
             individual congeners. The low-dose mixture and 6-OH-BDE-47
             groups exhibited reductions in body length and delayed
             maturation, specifically relating to swim bladder, fin, and
             pigmentation development. Reduced skeletal ossification was
             also observed in 6-OH-BDE-47-treated fish. Assessment of
             thyroid and osteochondral gene regulatory networks
             demonstrated significantly increased expression of genes
             that regulate skeletal development and thyroid hormones.
             Overall, these results indicate that exposures to
             PBDE/OH-BDE mixtures adversely impact zebrafish maturation
             during metamorphosis. Environ Toxicol Chem 2017;36:36-48. ©
             2016 SETAC.},
   Doi = {10.1002/etc.3535},
   Key = {fds330184}
}

@article{fds330275,
   Author = {Slotkin, TA and Stadler, A and Skavicus, S and Card, J and Ruff, J and Levin, ED and Seidler, FJ},
   Title = {Is There a Critical Period for the Developmental
             Neurotoxicity of Low-Level Tobacco Smoke
             Exposure?},
   Journal = {Toxicological Sciences},
   Volume = {155},
   Number = {1},
   Pages = {75-84},
   Year = {2017},
   Month = {January},
   url = {http://dx.doi.org/10.1093/toxsci/kfw180},
   Abstract = {Secondhand tobacco smoke exposure in pregnancy increases the
             risk of neurodevelopmental disorders. We evaluated in rats
             whether there is a critical period during which tobacco
             smoke extract (TSE) affects the development of acetylcholine
             and serotonin systems, prominent targets for adverse effects
             of nicotine and tobacco smoke. We simulated secondhand smoke
             exposure by administering TSE so as to produce nicotine
             concentrations one-tenth those in active smoking, with 3
             distinct, 10-day windows: premating, early gestation or late
             gestation. We conducted longitudinal evaluations in multiple
             brain regions, starting in early adolescence (postnatal day
             30) and continued to full adulthood (day 150). TSE exposure
             in any of the 3 windows impaired presynaptic cholinergic
             activity, exacerbated by a decrement in nicotinic
             cholinergic receptor concentrations. Although the adverse
             effects were seen for all 3 treatment windows, there was a
             distinct progression, with lowest sensitivity for premating
             exposure and higher sensitivity for gestational exposures.
             Serotonin receptors were also reduced by TSE exposure with
             the same profile: little effect with premating exposure,
             intermediate effect with early gestational exposure and
             large effect with late gestational exposure. As serotonergic
             circuits can offset the neurobehavioral impact of
             cholinergic deficits, these receptor changes were
             maladaptive. Thus, there is no single 'critical period' for
             effects of low-level tobacco smoke but there is differential
             sensitivity dependent upon the developmental stage at the
             time of exposure. Our findings reinforce the need to avoid
             secondhand smoke exposure not only during pregnancy, but
             also in the period prior to conception, or generally for
             women of childbearing age.},
   Doi = {10.1093/toxsci/kfw180},
   Key = {fds330275}
}

@article{fds330161,
   Author = {Rezvani, AH and Levin, ED and Cauley, M and Getachew, B and Tizabi,
             Y},
   Title = {Ketamine Differentially Attenuates Alcohol Intake in Male
             Versus Female Alcohol Preferring (P) Rats.},
   Journal = {Journal of Drug and Alcohol Research},
   Volume = {6},
   Pages = {1-6},
   Year = {2017},
   url = {http://dx.doi.org/10.4303/jdar/236030},
   Abstract = {Background: Although various pharmacological tools in
             combating addiction to alcohol are available, their efficacy
             is limited. Hence, there is a critical need for development
             of more effective medications. Recent advances in the field
             have identified the glutamatergic system as a potential
             novel target for intervention in addictive behaviors.
             Purpose: Hence, we evaluated the effects of acute
             administration of low (subanesthetic) doses of ketamine, an
             NMDA receptor antagonist, on alcohol intake and alcohol
             preference in both male and female rats. Study design: Adult
             alcohol preferring (P) rats were exposed to two-bottle
             choice (ethanol 10% and water) for at least three weeks
             following a nine-day training period and the effects of
             various doses of ketamine (5 mg/kg, 7.5 mg/kg, and 10 mg/kg,
             injected subcutaneously, SC) on consumption of alcohol over
             various time periods during a 24 h interval were measured.
             Results: Our results indicate that ketamine treatment
             significantly reduced both alcohol intake and preference in
             a time- and dose-dependent manner in both sexes. Moreover, a
             differential sensitivity between the sexes was observed.
             Thus, although alcohol intake was higher in males, female
             rats responded much more strongly to the highest dose of
             ketamine than males in the initial time periods. Conclusion:
             It is concluded that glutamatergic receptor manipulations
             may be of therapeutic potential in addiction to alcohol and
             that different sexes may respond differentially to such
             treatments.},
   Doi = {10.4303/jdar/236030},
   Key = {fds330161}
}

@article{fds320364,
   Author = {Slotkin, TA and Skavicus, S and Card, J and Levin, ED and Seidler,
             FJ},
   Title = {Diverse neurotoxicants target the differentiation of
             embryonic neural stem cells into neuronal and glial
             phenotypes.},
   Journal = {Toxicology},
   Volume = {372},
   Pages = {42-51},
   Year = {2016},
   Month = {November},
   url = {http://dx.doi.org/10.1016/j.tox.2016.10.015},
   Abstract = {The large number of compounds that needs to be tested for
             developmental neurotoxicity drives the need to establish in
             vitro models to evaluate specific neurotoxic endpoints. We
             used neural stem cells derived from rat neuroepithelium on
             embryonic day 14 to evaluate the impact of diverse toxicants
             on their ability to differentiate into glia and neurons: a
             glucocorticoid (dexamethasone), organophosphate insecticides
             (chlorpyrifos, diazinon, parathion), insecticides targeting
             the GABAA receptor (dieldrin, fipronil), heavy metals (Ni2+,
             Ag+), nicotine and tobacco smoke extract. We found three
             broad groupings of effects. One diverse set of compounds,
             dexamethasone, the organophosphate pesticides, Ni2+ and
             nicotine, suppressed expression of the glial phenotype while
             having little or no effect on the neuronal phenotype. The
             second pattern was restricted to the pesticides acting on
             GABAA receptors. These compounds promoted the glial
             phenotype and suppressed the neuronal phenotype. Notably,
             the actions of compounds eliciting either of these
             differentiation patterns were clearly unrelated to deficits
             in cell numbers: dexamethasone, dieldrin and fipronil all
             reduced cell numbers, whereas organophosphates and Ni2+ had
             no effect. The third pattern, shared by Ag+ and tobacco
             smoke extract, clearly delineated cytotoxicity,
             characterized by major cell loss with suppression of
             differentiation into both glial and neuronal phenotypes; but
             here again, there was some selectivity in that glia were
             suppressed more than neurons. Our results, from this survey
             with diverse compounds, point to convergence of
             neurotoxicant effects on a specific "decision node" that
             controls the emergence of neurons and glia from neural stem
             cells.},
   Doi = {10.1016/j.tox.2016.10.015},
   Key = {fds320364}
}

@article{fds320363,
   Author = {Petro, A and Sexton, HG and Miranda, C and Rastogi, A and Freedman, JH and Levin, ED},
   Title = {Persisting neurobehavioral effects of developmental copper
             exposure in wildtype and metallothionein 1 and 2 knockout
             mice.},
   Journal = {Bmc Pharmacology & Toxicology},
   Volume = {17},
   Number = {1},
   Pages = {55},
   Year = {2016},
   Month = {November},
   url = {http://dx.doi.org/10.1186/s40360-016-0096-3},
   Abstract = {BACKGROUND: Metallothioneins (MT) are small proteins, which
             are crucial for the distribution of heavy and transition
             metals. Previously, we found in mice that knockout of MT 1
             and 2 genes (MTKO) impaired spatial learning and potentiated
             the learning impairment caused by developmental mercury
             exposure. The current study examined the neurocognitive and
             neurochemical effects of MTKO with the developmental copper
             (Cu) supplementation. METHODS: Wildtype (WT) and MTKO mice
             were given supplemental Cu (0, 10 or 50 mg/l) in their
             drinking water during gestation and until weaning. When the
             mice were young adults they were trained on the win-shift
             8-arm radial maze test of spatial learning and memory. After
             cognitive testing, their brains were analyzed for
             norepinepherine, dopamine and serotonin levels. RESULTS: In
             the spatial learning test, wildtype mice showed the normal
             sex difference with males performing more accurately than
             the females. This effect was eliminated by MTKO and restored
             by moderate Cu supplementation during development. In
             neurochemical studies, MTKO caused a significant overall
             increase in serotonin in all of the regions studied: the
             frontal cortex, posterior cortex, hippocampus, striatum,
             midbrain, and brainstem. MTKO also caused a significant
             increase in norepinepherine in the brainstem and
             hippocampus. In wildtype mice, Cu supplementation during
             development caused a significant decline in dopamine and
             norepinepherine in the midbrain and dopamine in the frontal
             cortex. These effects were blocked by MTKO. CONCLUSIONS: The
             normal sex difference in spatial working memory accuracy,
             which was eliminated by MTKO, was restored by moderate
             copper supplementation. MTKO increased serotonin across all
             brain areas studied and increased norepinepherine only in
             the hippocampus and brainstem. MTKO blocked copper-induced
             decreases in dopamine and norepinepherine in the midbrain
             and dopamine in the frontal cortex.},
   Doi = {10.1186/s40360-016-0096-3},
   Key = {fds320363}
}

@article{fds330162,
   Author = {Rezvani, AH and Cauley, MC and Slade, S and Wells, C and Glick, S and Rose,
             JE and Levin, ED},
   Title = {Acute oral 18-methoxycoronaridine (18-MC) decreases both
             alcohol intake and IV nicotine self-administration in
             rats.},
   Journal = {Pharmacol Biochem Behav},
   Volume = {150-151},
   Pages = {153-157},
   Year = {2016},
   Month = {November},
   url = {http://dx.doi.org/10.1016/j.pbb.2016.10.010},
   Abstract = {The ibogaine derivative 18-methoxycoronaridine (18-MC) has
             been found to decrease self-administration of morphine,
             nicotine and alcohol in rats after systemic injection.
             However oral dosing is the preferred route clinically. The
             current study evaluated the effect of oral 18-MC dosing in
             rats on alcohol and nicotine self-administration. For the
             nicotine study, young adult female Sprague-Dawley rats were
             fitted with IV jugular infusion catheters and trained for
             nicotine self-administration in 45min. sessions. At weekly
             intervals they were administered by oral gavage doses of
             18-MC (0, 10, 20 and 40mg/kg) following a repeated measures
             counterbalanced design twice. Acute oral 18-MC, at the
             40mg/kg dosage, significantly reduced nicotine
             self-administration. There was a differential effect of
             18-MC with rats above or below the median level of nicotine
             self-administration during the pretreatment baseline
             performance. Rats with lower baseline performance showed a
             significant reduction in nicotine self-administration with
             the 40mg/kg dosage, while those in the higher baseline group
             did not show a significant effect of 18-MC. In alcohol
             studies, the effects of the same doses of 18-MC were tested
             in both male and female alcohol preferring (P) rats that had
             free access to water and alcohol (10% v/v) 6h/day. The
             results show that 18-MC dose-dependently reduced alcohol
             intake in both male and female rats. All doses caused
             significant reductions in alcohol self-administration. These
             data reinforce previous findings that 18-MC is significantly
             effective in reducing alcohol intake and nicotine
             self-administration. The finding that 18-MC is also
             effective orally makes it advantageous for further
             development as a possible new therapy for treating
             alcoholism as well as smoking addiction.},
   Doi = {10.1016/j.pbb.2016.10.010},
   Key = {fds330162}
}

@article{fds320365,
   Author = {Levin, ED and Hall, BJ and Chattopadhyay, A and Slade, S and Wells, C and Rezvani, AH and Rose, JE},
   Title = {Reduction of nicotine self-administration by chronic
             nicotine infusion with H1 histamine blockade in female
             rats.},
   Journal = {Psychopharmacology (Berl)},
   Volume = {233},
   Number = {15-16},
   Pages = {3009-3015},
   Year = {2016},
   Month = {August},
   url = {http://dx.doi.org/10.1007/s00213-016-4347-1},
   Abstract = {RATIONALE: Chronic nicotine infusion via transdermal patches
             has been widely shown to assist with smoking cessation. In
             particular, transdermal nicotine treatment prior to quitting
             smoking helps reduce ad libitum smoking and aids cessation
             Rose et al. (Nicotine Tob Res 11:1067-75, 2009). However,
             despite this success, the majority of smokers who use
             transdermal nicotine fail to permanently quit smoking.
             Additional treatments are needed. Tobacco addiction does not
             just depend on nicotinic receptor systems; a variety of
             neural systems are involved, including dopamine,
             norepinepherine, serotonin, and histamine. OBJECTIVES: Given
             the involvement of a variety of neural systems in the
             circuits of addiction, combination therapy may offer
             improved efficacy for successful smoking cessation beyond
             single treatments alone. We have found that pyrilamine, an
             H1 histamine antagonist, significantly decreases nicotine
             self-administration in rats. METHODS: The current study was
             conducted to confirm the effect of chronic nicotine infusion
             on ongoing nicotine self-administration and resumed access
             after enforced abstinence and to determine the interaction
             of chronic nicotine with an H1 antagonist treatment.
             RESULTS: Chronic nicotine infusion via osmotic minipump (2.5
             and 5 mg/kg/day for 28 days) significantly reduced
             nicotine self-administration in a dose-dependent manner.
             Chronic nicotine infusion also reduced the resumption of
             nicotine self-administration after enforced abstinence.
             Chronic pyrilamine infusion (25 mg/kg/day for 14 days)
             also significantly reduced nicotine self-administration.
             CONCLUSION: The combination of chronic nicotine and
             pyrilamine reduced nicotine self-administration to a greater
             extent than treatment with either drug alone.},
   Doi = {10.1007/s00213-016-4347-1},
   Key = {fds320365}
}

@article{fds316072,
   Author = {Hall, BJ and Cauley, M and Burke, DA and Kiany, A and Slotkin, TA and Levin, ED},
   Title = {Cognitive and Behavioral Impairments Evoked by Low-Level
             Exposure to Tobacco Smoke Components: Comparison with
             Nicotine Alone.},
   Journal = {Toxicological Sciences},
   Volume = {151},
   Number = {2},
   Pages = {236-244},
   Year = {2016},
   Month = {June},
   ISSN = {1096-6080},
   url = {http://dx.doi.org/10.1093/toxsci/kfw042},
   Abstract = {Active maternal smoking has adverse effects on
             neurobehavioral development of the offspring, with nicotine
             (Nic) providing much of the underlying causative mechanism.
             To determine whether the lower exposures caused by
             second-hand smoke are deleterious, we administered tobacco
             smoke extract (TSE) to pregnant rats starting preconception
             and continued through the second postnatal week,
             corresponding to all 3 trimesters of fetal brain
             development. Dosing was adjusted to produce maternal plasma
             Nic concentrations encountered with second-hand smoke, an
             order of magnitude below those seen in active smokers. We
             then compared TSE effects to those of an equivalent dose of
             Nic alone, and to a 10-fold higher Nic dose. Gestational
             exposure to TSE and Nic significantly disrupted cognitive
             and behavioral function in behavioral tests given during
             adolescence and adulthood (postnatal weeks 4-40), producing
             hyperactivity, working memory deficits, and impairments in
             emotional processing, even at the low exposure levels
             corresponding to second-hand smoke. Although TSE effects
             were highly correlated with those of Nic, the effects of TSE
             were much larger than could be attributed to just the Nic in
             the mixture. Indeed, TSE effects more closely resembled
             those of the 10-fold higher Nic levels, but still exceeded
             their magnitude. In combination with our earlier findings,
             this study thus completes the chain of causation to prove
             that second-hand smoke exposure causes neurodevelopmental
             deficits, originating in disruption of neurodifferentiation,
             leading to miswiring of neuronal circuits, and as shown
             here, culminating in behavioral dysfunction. As low level
             exposure to Nic alone produced neurobehavioral teratology,
             'harm reduction' Nic products do not abolish the potential
             for neurodevelopmental damage.},
   Doi = {10.1093/toxsci/kfw042},
   Key = {fds316072}
}

@article{fds316071,
   Author = {Levin, ED},
   Title = {Crumbling Infrastructure and Learning Impairment: A Call for
             Responsibility.},
   Journal = {Environ Health Perspect},
   Volume = {124},
   Number = {5},
   Pages = {A79},
   Year = {2016},
   Month = {May},
   ISSN = {0091-6765},
   url = {http://dx.doi.org/10.1289/EHP69},
   Doi = {10.1289/EHP69},
   Key = {fds316071}
}

@article{fds316073,
   Author = {Bao, X and Chandramohan, V and Reynolds, RP and Norton, JN and Wetsel,
             WC and Rodriguiz, RM and Aryal, DK and McLendon, RE and Levin, ED and Petry, NA and Zalutsky, MR and Burnett, BK and Kuan, C-T and Pastan, IH and Bigner, DD},
   Title = {Preclinical toxicity evaluation of a novel immunotoxin,
             D2C7-(scdsFv)-PE38KDEL, administered via intracerebral
             convection-enhanced delivery in rats.},
   Journal = {Invest New Drugs},
   Volume = {34},
   Number = {2},
   Pages = {149-158},
   Year = {2016},
   Month = {April},
   ISSN = {0167-6997},
   url = {http://dx.doi.org/10.1007/s10637-015-0318-3},
   Abstract = {D2C7-(scdsFv)-PE38KDEL (D2C7-IT) is a novel immunotoxin that
             reacts with wild-type epidermal growth factor receptor
             (EGFRwt) and mutant EGFRvIII proteins overexpressed in
             glioblastomas. This study assessed the toxicity of
             intracerebral administration of D2C7-IT to support an
             initial Food and Drug Administration Investigational New
             Drug application. After the optimization of the formulation
             and administration, two cohorts (an acute and chronic cohort
             necropsied on study days 5 and 34) of Sprague-Dawley (SD)
             rats (four groups of 5 males and 5 females) were infused
             with the D2C7-IT formulation at total doses of 0, 0.05, 0.1,
             0.4 μg (the acute cohort) and 0, 0.05, 0.1, 0.35 μg (the
             chronic cohort) for approximately 72 h by intracerebral
             convection-enhanced delivery using osmotic pumps. Mortality
             was observed in the 0.40 μg (5/10 rats) and 0.35 μg
             (4/10 rats) high-dose groups of each cohort. Body weight
             loss and abnormal behavior were only revealed in the rats
             treated with high doses of D2C7-IT. No dose-related effects
             were observed in clinical laboratory tests in either cohort.
             A gross pathologic examination of systemic tissues from the
             high-dose and control groups in both cohorts exhibited no
             dose-related or drug-related pathologic findings. Brain
             histopathology revealed the frequent occurrence of
             dose-related encephalomalacia, edema, and demyelination in
             the high-dose groups of both cohorts. In this study, the
             maximum tolerated dose of D2C7-IT was determined to be
             between 0.10 and 0.35 μg, and the no-observed-adverse-effect-level
             was 0.05 μg in SD rats. Both parameters were utilized to
             design the Phase I/II D2C7-IT clinical trial.},
   Doi = {10.1007/s10637-015-0318-3},
   Key = {fds316073}
}

@article{fds313800,
   Author = {Briggs, SA and Hall, BJ and Wells, C and Slade, S and Jaskowski, P and Morrison, M and Rezvani, AH and Rose, JE and Levin,
             ED},
   Title = {Dextromethorphan interactions with histaminergic and
             serotonergic treatments to reduce nicotine
             self-administration in rats.},
   Journal = {Pharmacol Biochem Behav},
   Volume = {142},
   Pages = {1-7},
   Year = {2016},
   Month = {March},
   ISSN = {0091-3057},
   url = {http://dx.doi.org/10.1016/j.pbb.2015.12.004},
   Abstract = {Combining effective treatments with diverse mechanisms of
             action for smoking cessation may provide better therapy by
             targeting multiple points of control in the neural circuits
             underlying addiction. Previous research in a rat model has
             shown that dextromethorphan, which has α3β4 nicotinic and
             NMDA glutamatergic antagonist actions, significantly
             decreases nicotine self-administration. We have found in the
             rat model that the H1 histamine antagonist pyrilamine and
             the serotonin 5HT2C agonist lorcaserin also significantly
             reduce nicotine self-administration. The current studies
             were conducted to determine the interactive effects of
             dextromethorphan with pyrilamine and lorcaserin on nicotine
             self-administration in rats. Young adult female rats were
             fitted with jugular IV catheters and trained to
             self-administer a nicotine infusion dose of
             0.03-mg/kg/infusion. In an initial dose-effect function
             study of dextromethorphan, we found a monotonic decrease in
             nicotine self-administration over a dose range of 1 to
             30-mg/kg with the lowest effective dose of 3-mg/kg. Then,
             with two separate cohorts of rats, dextromethorphan (0, 3.3,
             and 10-mg/kg) interactions with pyrilamine (0, 4.43, and
             13.3-mg/kg) were investigated as well as interactions with
             lorcaserin (0, 0.3125 and 0.625-mg/kg). In the
             pyrilamine-dextromethorphan interaction study, an acute dose
             of pyrilamine (13.3-mg/kg) as well as an acute dose of
             dextromethorphan caused a significant decrease in nicotine
             self-administration. There were mutually augmenting effects
             of these two drugs. The combination of dextromethorphan
             (10-mg/kg) and pyrilamine (13.3-mg/kg) significantly lowered
             nicotine self-administration relative to either 10-mg/kg of
             dextromethorphan alone (p<0.05) or 13.3-mg/kg of pyrilamine
             alone (p<0.0005). In the lorcaserin-dextromethorphan study,
             an acute dose of lorcaserin (0.312-mg/kg) as well as an
             acute dose of dextromethorphan (10-mg/kg) caused a
             significant decrease in nicotine self-administration
             replicating previous findings. Augmenting interactions were
             observed with dextromethorphan and pyrilamine as well as
             lorcaserin. These findings suggest that combination therapy
             may be more effective smoking cessation treatments than
             monotherapy.},
   Doi = {10.1016/j.pbb.2015.12.004},
   Key = {fds313800}
}

@article{fds313802,
   Author = {Bailey, JM and Oliveri, AN and Karbhari, N and Brooks, RAJ and De La
             Rocha and AJ and Janardhan, S and Levin, ED},
   Title = {Persistent behavioral effects following early life exposure
             to retinoic acid or valproic acid in zebrafish.},
   Journal = {Neurotoxicology},
   Volume = {52},
   Pages = {23-33},
   Year = {2016},
   Month = {January},
   ISSN = {0161-813X},
   url = {http://dx.doi.org/10.1016/j.neuro.2015.10.001},
   Abstract = {BACKGROUND: Moderate to severe dysregulation in retinoid
             signaling during early development is associated with a
             constellation of physical malformations and/or neural tube
             defects, including spina bifida. It is thought that more
             subtle dysregulation of this system, which might be
             achievable via dietary (i.e. hypervitaminosis A) or
             pharmacological (i.e. valproic acid) exposure in humans,
             will manifest on behavioral domains including sociability,
             without overt physical abnormalities. METHODS: During early
             life, zebrafish were exposed to low doses of two chemicals
             that disrupt retinoid signaling. From 0 to 5dpf, larvae were
             reared in aqueous solutions containing retinoic acid (0,
             0.02, 0.2 or 2nM) or valproic acid (0, 0.5, 5.0 or 50μM).
             One cohort of zebrafish was assessed using a locomotor
             activity screen at 6-dpf; another was reared to adulthood
             and assessed using a neurobehavioral test battery (startle
             habituation, novel tank exploration, shoaling, and predator
             escape/avoidance). RESULTS: There was no significant
             increase in the incidence of physical malformation among
             exposed fish compared to controls. Both retinoic acid and
             valproic acid exposures during development disrupted larval
             activity with persisting behavioral alterations later in
             life, primarily manifesting as decreased social affiliation.
             CONCLUSIONS: Social behavior and some aspects of motor
             function were altered in exposed fish; the importance of
             examining emotional or psychological consequences of early
             life exposure to retinoid acting chemicals is
             discussed.},
   Doi = {10.1016/j.neuro.2015.10.001},
   Key = {fds313802}
}

@article{fds320366,
   Author = {Rezvani, AH and Levin, ED and Wells, C and Slade, S and Morrison, M and Marshall, L and Morris, M and Confino, J and Allenby, C and Lumeng,
             L},
   Title = {Different lines of rats selectively-bred for high
             alcohol-drinking demonstrate disparate preferences for
             nicotine self-administration},
   Journal = {Journal of Drug and Alcohol Research},
   Volume = {2016},
   Number = {5},
   Pages = {1-9},
   Publisher = {Ashdin Publishing},
   Year = {2016},
   Month = {January},
   url = {http://dx.doi.org/10.4303/jdar/235972},
   Abstract = {© 2016 Amir H. Rezvani et al. Background. Alcohol and
             nicotine are commonly coabused. The search for a common core
             of neural, behavioral, and genetic factors underlying
             addiction has been the goal of addiction research. Purpose.
             Genetic predisposition to high alcohol intake has been
             studied in rats by selectively breeding rats that have high
             preference for alcohol. The current experiments were
             conducted to determine if the level of intravenous nicotine
             administration for the various lines of alcohol-preferring
             rats differs from that for nonalcohol-preferring controls.
             Study design. Adult alcohol-naïve selectively-bred
             alcohol-preferring male rats from four lines (P, AA, HAD-1,
             sP) and their control nonalcohol-preferring rats (NP, ANA,
             LAD-1, sNP) were trained and given access to self-administer
             nicotine (0.03mg/kg/infusion). Results. The results show
             that the P rats selfadministered significantly more nicotine
             than NP rats. In contrast, there were no significant
             differences in nicotine self-administration between the sP
             and sNP or the AA and ANA rats. Unexpectedly, high
             alcohol-drinking HAD-1 rats self-administered significantly
             less nicotine than low alcohol-drinking LAD-1 rats.
             Conclusion. This suggests that some genetic factors that
             underlie high-alcohol intake have more general effects in
             promoting high nicotine intake tendencies, while other
             genetic factors are more specific to only heavy
             drinking.},
   Doi = {10.4303/jdar/235972},
   Key = {fds320366}
}

@article{fds313801,
   Author = {Brown, DR and Bailey, JM and Oliveri, AN and Levin, ED and Di Giulio,
             RT},
   Title = {Developmental exposure to a complex PAH mixture causes
             persistent behavioral effects in naive Fundulus heteroclitus
             (killifish) but not in a population of PAH-adapted
             killifish.},
   Journal = {Neurotoxicol Teratol},
   Volume = {53},
   Pages = {55-63},
   Year = {2016},
   Month = {January},
   ISSN = {0892-0362},
   url = {http://dx.doi.org/10.1016/j.ntt.2015.10.007},
   Abstract = {Acute exposures to some individual polycyclic aromatic
             hydrocarbons (PAHs) and complex PAH mixtures are known to
             cause cardiac malformations and edema in the developing fish
             embryo. However, the heart is not the only organ impacted by
             developmental PAH exposure. The developing brain is also
             affected, resulting in lasting behavioral dysfunction. While
             acute exposures to some PAHs are teratogenically lethal in
             fish, little is known about the later life consequences of
             early life, lower dose subteratogenic PAH exposures. We
             sought to determine and characterize the long-term
             behavioral consequences of subteratogenic developmental PAH
             mixture exposure in both naive killifish and PAH-adapted
             killifish using sediment pore water derived from the
             Atlantic Wood Industries Superfund Site. Killifish offspring
             were embryonically treated with two low-level PAH mixture
             dilutions of Elizabeth River sediment extract (ERSE) (TPAH
             5.04 μg/L and 50.4 μg/L) at 24h post fertilization.
             Following exposure, killifish were raised to larval,
             juvenile, and adult life stages and subjected to a series of
             behavioral tests including: a locomotor activity test (4
             days post-hatch), a sensorimotor response tap/habituation
             test (3 months post hatch), and a novel tank diving and
             exploration test (3months post hatch). Killifish were also
             monitored for survival at 1, 2, and 5 months over 5-month
             rearing period. Developmental PAH exposure caused short-term
             as well as persistent behavioral impairments in naive
             killifish. In contrast, the PAH-adapted killifish did not
             show behavioral alterations following PAH exposure. PAH
             mixture exposure caused increased mortality in reference
             killifish over time; yet, the PAH-adapted killifish, while
             demonstrating long-term rearing mortality, had no
             significant changes in mortality associated with ERSE
             exposure. This study demonstrated that early embryonic
             exposure to PAH-contaminated sediment pore water caused
             long-term locomotor and behavioral alterations in killifish,
             and that locomotor alterations could be observed in early
             larval stages. Additionally, our study highlights the
             resistance to behavioral alterations caused by low-level PAH
             mixture exposure in the adapted killifish population.
             Furthermore, this is the first longitudinal behavioral study
             to use killifish, an environmentally important estuarine
             teleost fish, and this testing framework can be used for
             future contaminant assessment.},
   Doi = {10.1016/j.ntt.2015.10.007},
   Key = {fds313801}
}

@article{fds274169,
   Author = {Bailey, JM and Oliveri, AN and Levin, ED},
   Title = {Pharmacological analyses of learning and memory in zebrafish
             (Danio rerio).},
   Journal = {Pharmacol Biochem Behav},
   Volume = {139 Pt B},
   Pages = {103-111},
   Year = {2015},
   Month = {December},
   ISSN = {0091-3057},
   url = {http://dx.doi.org/10.1016/j.pbb.2015.03.006},
   Abstract = {Over the last decade, zebrafish (Danio rerio) have become
             valuable as a complementary model in behavioral
             pharmacology, opening a new avenue for understanding the
             relationships between drug action and behavior. This species
             offers a useful intermediate approach bridging the gap
             between in vitro studies and traditional mammalian models.
             Zebrafish offer great advantages of economy compared to
             their rodent counterparts, their complex brains and
             behavioral repertoire offer great translational potential
             relative to in vitro models. The development and validation
             of a variety of tests to measure behavior, including
             cognition, in zebrafish have set the stage for the use of
             this animal for behavioral pharmacology studies. This has
             led to research into the basic mechanisms of cognitive
             function as well as screening for potential
             cognition-improving drug therapies, among other lines of
             research. As with all models, zebrafish have limitations,
             which span pharmacokinetic challenges to difficulties
             quantifying behavior. The use, efficacy and limitations
             associated with a zebrafish model of cognitive function are
             discussed in this review, within the context of behavioral
             pharmacology.},
   Doi = {10.1016/j.pbb.2015.03.006},
   Key = {fds274169}
}

@article{fds274170,
   Author = {Hall, BJ and Slade, S and Allenby, C and Kutlu, MG and Levin,
             ED},
   Title = {Neuro-anatomic mapping of dopamine D1 receptor involvement
             in nicotine self-administration in rats.},
   Journal = {Neuropharmacology},
   Volume = {99},
   Pages = {689-695},
   Year = {2015},
   Month = {December},
   ISSN = {0028-3908},
   url = {http://dx.doi.org/10.1016/j.neuropharm.2015.03.005},
   Abstract = {Dopaminergic signaling has long been known to be a critical
             factor in nicotine addiction, as well as other drugs of
             abuse. Dopaminergic projections from the VTA to the nucleus
             accumbens and prefrontal cortex have been well established
             to be critical to the reinforcing effects of these drugs.
             However, other projections of dopamine neurons are likely to
             have significant roles in this process. Also, the relative
             contributions of D1 and D2 dopamine receptors in drug
             addiction and its treatment remain to be fully understood.
             In this study, we examined the effects of blocking D1 and D2
             receptors in the nucleus accumbens shell (AcS), anterior
             cingulate cortex (ACC), and parietal association cortex
             (PtA) on nicotine self-administration in rats. Female
             Sprague-Dawley rats were fitted with jugular catheters and
             allowed to self-administer nicotine (0.03 mg/kg/infusion)
             on an FR1 schedule. Rats were fitted with bilateral infusion
             cannulae to allow infusion of D1 or D2 antagonists
             (SCH-23390 or haloperidol) into each targeted brain area.
             Acute local infusions of SCH-23390 (1-4 μg/side) into the
             AcS and PtA significantly reduced nicotine
             self-administration by up to 75%. SCH-23390 infusion into
             the ACC was less effective with only suggestive
             non-significant reductions of nicotine self-administration.
             Acute, local infusions of haloperidol (0.5-2 μg/side) in
             any of the brain regions targeted did not have significant
             effects on nicotine self-administration. These results
             demonstrate a more significant role for D1 receptor
             mechanisms in the process of nicotine reinforcement and help
             provide a more detailed neuroanatomic map of nicotine
             dependence in the brain.},
   Doi = {10.1016/j.neuropharm.2015.03.005},
   Key = {fds274170}
}

@article{fds316074,
   Author = {Levin, ED and Kalueff, AV and Gerlai, RT},
   Title = {Perspectives on zebrafish neurobehavioral
             pharmacology.},
   Journal = {Pharmacol Biochem Behav},
   Volume = {139 Pt B},
   Pages = {93},
   Year = {2015},
   Month = {December},
   ISSN = {0091-3057},
   url = {http://dx.doi.org/10.1016/j.pbb.2015.11.007},
   Doi = {10.1016/j.pbb.2015.11.007},
   Key = {fds316074}
}

@article{fds274164,
   Author = {Oliveri, AN and Bailey, JM and Levin, ED},
   Title = {Developmental exposure to organophosphate flame retardants
             causes behavioral effects in larval and adult
             zebrafish.},
   Journal = {Neurotoxicol Teratol},
   Volume = {52},
   Number = {Pt B},
   Pages = {220-227},
   Year = {2015},
   Month = {November},
   ISSN = {0892-0362},
   url = {http://dx.doi.org/10.1016/j.ntt.2015.08.008},
   Abstract = {BACKGROUND: Organophosphate flame retardants (OPFRs) have
             grown in usage since concerns about the health effects of
             the previously used polybrominated flame retardants led to
             their being phased out. The potential for OPFRs to cause
             adverse health effects of their own is still unexamined.
             Because of their structural similarities to organophosphate
             pesticides, which have themselves been heavily researched
             and shown to be neurobehavioral teratogens, we investigated
             the possibility that developmental exposure to two OPFRs,
             triphenyl phosphate (TPHP), and tris(1,3-dichloroisopropyl)phosphate
             (TDCIPP) might lead to behavioral impairment across the
             lifespan, as has been observed with the organophosphate
             pesticide chlorpyrifos. METHODS: Zebrafish were exposed to
             0.03 or 0.3 μM of TPHP, TDCIPP, or chlorpyrifos from 0 to 5
             days post fertilization. Vehicle control consisted of 0.03%
             solution of DMSO. At 6 days post fertilization, larvae were
             tested on a locomotor assay. Separate cohorts of 6 day old
             larvae that were not tested on the larval assay were allowed
             to grow to adulthood. At 12 weeks post fertilization, these
             adult zebrafish were tested on a battery of behavioral
             assays that included tests of novel environment exploration,
             startle habituation, social affiliation, and predator
             escape. RESULTS: Developmental exposure altered zebrafish
             behavior across the lifespan. Larval zebrafish exposed to
             the 0.03 μM doses of chlorpyrifos or TDCIPP exhibited
             significant (p<0.05) hyperactivity in the locomotor assay.
             Organophosphate exposure significantly (p<0.05) altered the
             time course of adult zebrafish behavior in the novel
             environment, startle habituation, and social affiliation
             assays. Predator escape behavior was significantly (p<0.05)
             reduced in fish exposed to the 0.3 μM dose of TDCIPP.
             Exposure also caused hyperactivity in adult fish, with fish
             exposed to the 0.3 μM dose of TDCIPP exhibiting
             significantly (p<0.05) elevated locomotor behavior in the
             novel environment assay. DISCUSSION: Early developmental
             exposure to OPFRs produced behavioral impairment that
             persisted into adulthood. These findings support broader
             research investigating the role of organophosphate
             compounds, including the OPFRs used here, in developmental
             neurotoxicity.},
   Doi = {10.1016/j.ntt.2015.08.008},
   Key = {fds274164}
}

@article{fds274174,
   Author = {Macaulay, LJ and Bailey, JM and Levin, ED and Stapleton,
             HM},
   Title = {Persisting effects of a PBDE metabolite, 6-OH-BDE-47, on
             larval and juvenile zebrafish swimming behavior.},
   Journal = {Neurotoxicol Teratol},
   Volume = {52},
   Number = {Pt B},
   Pages = {119-126},
   Publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
   Year = {2015},
   Month = {November},
   ISSN = {0892-0362},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000367108400003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Abstract = {Polybrominated diphenyl ethers (PBDEs) are persistent
             organic pollutants that are widely detected in the
             environment, biota, and humans. In mammals, PBDEs can be
             oxidatively metabolized to form hydroxylated polybrominated
             diphenyl ethers (OH-BDEs). While studies have examined
             behavioral deficits or alterations induced by exposure to
             PBDEs in both rodents and fish, no study to date has
             explored behavioral effects from exposure to OH-BDEs, which
             have been shown to have greater endocrine disrupting
             potential compared to PBDEs. In the present study, zebrafish
             (Danio rerio) were exposed during embryonic and larval
             development (0-6 days post fertilization, dpf) to a PBDE
             metabolite, 6-hydroxy, 2,2',4,4' tetrabromodiphenyl ether
             (10-50 nM) and then examined for short and long-term
             behavioral effects. Exposed zebrafish tested as larvae (6
             dpf) showed an altered swimming response to light-dark
             transitions, exhibiting hypoactivity in light periods
             compared to control fish. When fish exposed from 0-6 dpf
             were tested as juveniles (45 dpf), they showed an increased
             fear response and hyperactivity in response to tests of
             novel environment exploration and habituation learning.
             These results demonstrate that early life exposure to a PBDE
             metabolite can have immediate or later life (more than a
             month after exposure) effects on activity levels,
             habituation, and fear/anxiety.},
   Doi = {10.1016/j.ntt.2015.05.002},
   Key = {fds274174}
}

@article{fds274175,
   Author = {Levin, ED},
   Title = {Learning about cognition risk with the radial-arm maze in
             the developmental neurotoxicology battery.},
   Journal = {Neurotoxicol Teratol},
   Volume = {52},
   Number = {Pt A},
   Pages = {88-92},
   Year = {2015},
   Month = {November},
   ISSN = {0892-0362},
   url = {http://dx.doi.org/10.1016/j.ntt.2015.05.007},
   Abstract = {Cognitive dysfunction has been found in epidemiological
             studies to be among the most sensitive impairments
             associated with developmental exposure to a variety of
             environmental contaminants from heavy metals to
             polyhalogenated hydrocarbons and pesticides. These chemicals
             have been also shown to impair cognitive function after
             developmental exposure in experimental animal models. The
             radial-arm maze (RAM) has proven to be a sensitive and
             reliable way to assess both learning and memory in a variety
             of species, most often in rats and mice. The RAM is a very
             adaptable test method that takes advantage of rodents'
             instinct to explore new places in the environment to forage.
             That is, rodents do not need to be trained to run through
             the maze; they will normally do this from the initial
             session of testing. Training with differential reinforcement
             for arm choices provides a more rigorous test of learning
             and memory. The RAM is quite adaptable for assessing various
             aspects of cognition. Although the RAM has been mostly used
             to assess spatial learning and memory, it can be configured
             to assess non-spatial memory as well. Both working and
             reference memory can be easily distinguished. The RAM can be
             run with both appetitive (food reinforced) and aversive
             (water escape) motivators. The RAM has been found to be
             sensitive to a wide variety of developmental toxicants
             including heavy metals such as mercury and pesticides such
             as chlorpyrifos. There is an extremely rich literature
             especially with rats showing the effects of many types of
             brain lesions and drug effects so that the participation of
             a wide variety of neural systems in RAM performance is
             known. These systems, notably the hippocampus and frontal
             cortex, and acetylcholine and glutamate neurotransmitter
             systems, are the same neural systems that have been shown in
             humans to be critical for learning and memory. This
             considerably aids the interpretation of neurobehavioral
             toxicity studies.},
   Doi = {10.1016/j.ntt.2015.05.007},
   Key = {fds274175}
}

@article{fds274178,
   Author = {Bailey, JM and Levin, ED},
   Title = {Neurotoxicity of FireMaster 550® in zebrafish (Danio
             rerio): Chronic developmental and acute adolescent
             exposures.},
   Journal = {Neurotoxicol Teratol},
   Volume = {52},
   Number = {Pt B},
   Pages = {210-219},
   Year = {2015},
   Month = {November},
   ISSN = {0892-0362},
   url = {http://dx.doi.org/10.1016/j.ntt.2015.07.001},
   Abstract = {BACKGROUND: FireMaster® 550 (FM 550) is the second most
             commonly used flame retardant (FR) product in consumer goods
             and has been detected in household dust samples. However,
             neurobehavioral effects associated with exposure have not
             been characterized in detail. We investigated the behavioral
             effects of FM 550 in zebrafish to facilitate the integration
             of the cellular and molecular effects of FM 550 with its
             behavioral consequences. The effects of developmental FM 550
             exposure on zebrafish larvae swimming shortly after the end
             of exposure as well as the persisting effects of this
             exposure on adolescent behavior were studied. In addition,
             the acute effects of FM 550 on behavior with exposure during
             adolescence in zebrafish were studied. METHODS:
             Developmental exposure to 0, 0.01, 0.1 or 1 mg/L of FM 550
             via immersion spanned 0-5 days post fertilization, with
             larval testing on day 6 and adolescent testing on days
             40-45. Acute adolescent (45 dpf) exposure was to 0, 1.0 or
             3.0 mg/L of FM 550 via immersion, for 24 h, with testing 2 h
             or 1 week later. The vehicle condition was colony tank water
             with .0004% (developmental) or .0012% (adolescent) DMSO.
             Zebrafish behavior was characterized across several domains
             including learning, social affiliation, sensorimotor
             function, predator escape, and novel environment
             exploration. RESULTS: Persisting effects of developmental FM
             550 exposure included a significant (p<0.01) reduction in
             social behavior among all dose groups. Acute FM 550 exposure
             during adolescence caused hypoactivity and reduced social
             behavior (p's<0.05) when the fish were tested 2 h after
             exposure. These effects were attenuated at the 1 week post
             exposure testing point DISCUSSION: Taken together, these
             data indicate that FM 550 may cause persisting
             neurobehavioral alterations to social behavior in the
             absence of perturbations along other behavioral domains and
             that developmental exposure is more costly to the organism
             than acute adolescent exposure.},
   Doi = {10.1016/j.ntt.2015.07.001},
   Key = {fds274178}
}

@article{fds274177,
   Author = {Levin, ED and Wells, C and Johnson, JE and Rezvani, AH and Bymaster, FP and Rose, JE},
   Title = {Amitifadine, a triple monoamine re-uptake inhibitor, reduces
             nicotine self-administration in female rats.},
   Journal = {Eur J Pharmacol},
   Volume = {764},
   Pages = {30-37},
   Year = {2015},
   Month = {October},
   ISSN = {0014-2999},
   url = {http://dx.doi.org/10.1016/j.ejphar.2015.06.041},
   Abstract = {A wider diversity of drug treatments to aid smoking
             cessation is needed to help tailor the most efficacious
             treatment for different types of smokers. This study was
             conducted to determine whether amitifadine, which inhibits
             re-uptake of dopamine, norepinephrine and serotonin, would
             decrease nicotine self-administration at doses that do not
             cause adverse side effects. Adult female Sprague-Dawley rats
             were trained to self-administer nicotine intravenous (IV)
             and were given acute doses of amitifadine in a repeated
             measures counterbalanced design. Effects of amitifadine on
             locomotor activity and food motivated responding were also
             evaluated. Chronic amitifadine effects were also examined.
             The 30 mg/kg amitifadine dose significantly reduced nicotine
             self-administration. The 5 and 10 mg/kg doses reduced
             nicotine self-administration during the first 15 min of the
             session when the greatest amount of nicotine was
             self-administered. The 30 mg/kg amitifadine dose, but not
             the lower doses caused a significant reduction in locomotor
             activity averaged over the one-hour session and reduced food
             motivated responding. The 10 mg/kg dose caused hypoactivity
             at the beginning of the session, but 5 mg/kg did not cause
             any hypoactivity. The effects of chronic amitifadine
             treatment (10 mg/kg) over the course of 15 sessions was also
             determined. Amitifadine caused a significant reduction in
             nicotine self-administration, which was not seen to diminish
             over two consecutive weeks of treatment and a week after
             enforced abstinence. Amitifadine significantly reduced
             nicotine self-administration. This prompts further research
             to determine if amitifadine might be an effective treatment
             for smoking cessation.},
   Doi = {10.1016/j.ejphar.2015.06.041},
   Key = {fds274177}
}

@article{fds274163,
   Author = {Massarsky, A and Jayasundara, N and Bailey, JM and Oliveri, AN and Levin, ED and Prasad, GL and Di Giulio and RT},
   Title = {Teratogenic, bioenergetic, and behavioral effects of
             exposure to total particulate matter on early development of
             zebrafish (Danio rerio) are not mimicked by
             nicotine.},
   Journal = {Neurotoxicol Teratol},
   Volume = {51},
   Pages = {77-88},
   Year = {2015},
   Month = {September},
   ISSN = {0892-0362},
   url = {http://dx.doi.org/10.1016/j.ntt.2015.09.006},
   Abstract = {Cigarette smoke has been associated with a number of
             pathologies; however, the mechanisms leading to
             developmental effects are yet to be fully understood. The
             zebrafish embryo is regarded as a 'bridge model'; however,
             not many studies examined its applicability to cigarette
             smoke toxicity. This study examined the effects of total
             particulate matter (TPM) from 3R4F reference cigarettes on
             the early development of zebrafish (Danio rerio). Zebrafish
             embryos were exposed to two concentrations of TPM (0.4 and
             1.4 μg/mL equi-nicotine units) or nicotine at equivalent
             doses. The exposures began at 2h post-fertilization (hpf)
             and lasted until 96 hpf. Several physiological parameters
             were assessed during or after the exposure. We show that TPM
             increased mortality, delayed hatching, and increased the
             incidence of deformities in zebrafish. TPM exposure also
             increased the incidence of hemorrhage and disrupted the
             angiogenesis of the major vessels in the brain. Moreover,
             TPM exposure reduced the larval body length, decreased the
             heart rate, and reduced the metabolic rate. Biomarkers of
             xenobiotic metabolism and oxidative stress were also
             affected. TPM-exposed zebrafish also differed behaviorally:
             at 24 hpf the embryos had a higher frequency of spontaneous
             contractions and at 144 hpf the larvae displayed swimming
             hyperactivity. This study demonstrates that TPM disrupts
             several aspects of early development in zebrafish. The
             effects reported for TPM were not attributable to nicotine,
             since embryos treated with nicotine alone did not differ
             significantly from the control group. Collectively, our work
             illustrates the utility of zebrafish as an alternative model
             to evaluate the toxic effects of cigarette smoke
             constituents.},
   Doi = {10.1016/j.ntt.2015.09.006},
   Key = {fds274163}
}

@article{fds274176,
   Author = {Slotkin, TA and Skavicus, S and Card, J and Stadler, A and Levin, ED and Seidler, FJ},
   Title = {Developmental Neurotoxicity of Tobacco Smoke Directed Toward
             Cholinergic and Serotonergic Systems: More Than Just
             Nicotine.},
   Journal = {Toxicological Sciences},
   Volume = {147},
   Number = {1},
   Pages = {178-189},
   Year = {2015},
   Month = {September},
   ISSN = {1096-6080},
   url = {http://dx.doi.org/10.1093/toxsci/kfv123},
   Abstract = {Tobacco smoke contains thousands of compounds in addition to
             nicotine, a known neuroteratogen. We evaluated the
             developmental neurotoxicity of tobacco smoke extract (TSE)
             administered to pregnant rats starting preconception and
             continued through the second postnatal week. We simulated
             nicotine concentrations encountered with second-hand smoke,
             an order of magnitude below those seen in active smokers,
             and compared TSE with an equivalent dose of nicotine alone,
             and to a 10-fold higher nicotine dose. We conducted
             longitudinal evaluations in multiple brain regions, starting
             in adolescence (postnatal day 30) and continued to full
             adulthood (day 150). TSE exposure impaired presynaptic
             cholinergic activity, exacerbated by a decrement in
             nicotinic cholinergic receptor concentrations. Although both
             nicotine doses produced presynaptic cholinergic deficits,
             these were partially compensated by hyperinnervation and
             receptor upregulation, effects that were absent with TSE.
             TSE also produced deficits in serotonin receptors in females
             that were not seen with nicotine. Regression analysis showed
             a profound sex difference in the degree to which nicotine
             could account for overall TSE effects: whereas the 2
             nicotine doses accounted for 36%-46% of TSE effects in
             males, it accounted for only 7%-13% in females. Our results
             show that the adverse effects of TSE on neurodevelopment
             exceed those that can be attributed to just the nicotine
             present in the mixture, and further, that the sensitivity
             extends down to levels commensurate with second-hand smoke
             exposure. Because nicotine itself evoked deficits at low
             exposures, "harm reduction" nicotine products do not
             eliminate the potential for neurodevelopmental
             damage.},
   Doi = {10.1093/toxsci/kfv123},
   Key = {fds274176}
}

@article{fds274172,
   Author = {Larrauri, JA and Burke, DA and Hall, BJ and Levin,
             ED},
   Title = {Role of nicotinic receptors in the lateral habenula in the
             attenuation of amphetamine-induced prepulse inhibition
             deficits of the acoustic startle response in
             rats.},
   Journal = {Psychopharmacology (Berl)},
   Volume = {232},
   Number = {16},
   Pages = {3009-3017},
   Year = {2015},
   Month = {August},
   ISSN = {0033-3158},
   url = {http://dx.doi.org/10.1007/s00213-015-3940-z},
   Abstract = {RATIONALE: Prepulse inhibition (PPI) refers to the reduction
             of the startle response magnitude when a startling stimulus
             is closely preceded by a weak stimulus. PPI is commonly used
             to measure sensorimotor gating. In rats, the PPI reduction
             induced by the dopamine agonist apomorphine can be reversed
             by systemic administration of nicotine. A high concentration
             of nicotinic receptors is found in the lateral habenula
             (LHb), an epithalamic structure with efferent projections to
             brain regions involved in the modulation of PPI, which has
             been shown to regulate the activity of midbrain dopamine
             neurons. OBJECTIVES: The prospective role of nicotinic
             receptors in the LHb in the regulation of PPI was assessed
             in this study, using different pharmacological models of
             sensorimotor gating deficits. METHODS: Interactions between
             systemic amphetamine and haloperidol and intra-LHb infusions
             of mecamylamine (10 μg/side) or nicotine (30 μg/side) on
             PPI were analyzed in Experiments 1 and 2. Intra-LHb
             infusions of different nicotine doses (25, and 50 μg/side)
             and their interactions with systemic administration of
             amphetamine or dizocilpine on PPI were examined in
             Experiments 3 and 4. RESULTS: Infusions of nicotine into the
             LHb dose-dependently attenuated amphetamine-induced PPI
             deficits but had no effect on PPI disruptions caused by
             dizocilpine. Intra-LHb mecamylamine infusions did not affect
             PPI nor interact with dopaminergic manipulations.
             CONCLUSIONS: These results are congruent with previous
             reports of systemic nicotine effects on PPI, suggesting a
             role of the LHb in the attenuation of sensorimotor gating
             deficits caused by the hyperactivity of dopamine
             systems.},
   Doi = {10.1007/s00213-015-3940-z},
   Key = {fds274172}
}

@article{fds274171,
   Author = {Slotkin, TA and Skavicus, S and Card, J and Levin, ED and Seidler,
             FJ},
   Title = {Amelioration strategies fail to prevent tobacco smoke
             effects on neurodifferentiation: Nicotinic receptor
             blockade, antioxidants, methyl donors.},
   Journal = {Toxicology},
   Volume = {333},
   Pages = {63-75},
   Year = {2015},
   Month = {July},
   ISSN = {0300-483X},
   url = {http://dx.doi.org/10.1016/j.tox.2015.04.005},
   Abstract = {Tobacco smoke exposure is associated with neurodevelopmental
             disorders. We used neuronotypic PC12 cells to evaluate the
             mechanisms by which tobacco smoke extract (TSE) affects
             neurodifferentiation. In undifferentiated cells, TSE
             impaired DNA synthesis and cell numbers to a much greater
             extent than nicotine alone; TSE also impaired cell viability
             to a small extent. In differentiating cells, TSE enhanced
             cell growth at the expense of cell numbers and promoted
             emergence of the dopaminergic phenotype. Nicotinic receptor
             blockade with mecamylamine was ineffective in preventing the
             adverse effects of TSE and actually enhanced the effect of
             TSE on the dopamine phenotype. A mixture of antioxidants
             (vitamin C, vitamin E, N-acetyl-l-cysteine) provided partial
             protection against cell loss but also promoted loss of the
             cholinergic phenotype in response to TSE. Notably, the
             antioxidants themselves altered neurodifferentiation,
             reducing cell numbers and promoting the cholinergic
             phenotype at the expense of the dopaminergic phenotype, an
             effect that was most prominent for N-acetyl-l-cysteine.
             Treatment with methyl donors (vitamin B12, folic acid,
             choline) had no protectant effect and actually enhanced the
             cell loss evoked by TSE; they did have a minor, synergistic
             interaction with antioxidants protecting against TSE effects
             on growth. Thus, components of tobacco smoke perturb
             neurodifferentiation through mechanisms that cannot be
             attributed to the individual effects of nicotine, oxidative
             stress or interference with one-carbon metabolism.
             Consequently, attempted amelioration strategies may be
             partially effective at best, or, as seen here, can actually
             aggravate injury by interfering with normal developmental
             signals and/or by sensitizing cells to TSE effects on
             neurodifferentiation.},
   Doi = {10.1016/j.tox.2015.04.005},
   Key = {fds274171}
}

@article{fds274173,
   Author = {Crosby, EB and Bailey, JM and Oliveri, AN and Levin,
             ED},
   Title = {Neurobehavioral impairments caused by developmental
             imidacloprid exposure in zebrafish.},
   Journal = {Neurotoxicol Teratol},
   Volume = {49},
   Pages = {81-90},
   Year = {2015},
   Month = {May},
   ISSN = {0892-0362},
   url = {http://dx.doi.org/10.1016/j.ntt.2015.04.006},
   Abstract = {BACKGROUND: Neonicotinoid insecticides are becoming more
             widely applied as organophosphate (OP) insecticides are
             decreasing in use. Because of their relative specificity to
             insect nicotinic receptors, they are thought to have reduced
             risk of neurotoxicity in vertebrates. However, there is
             scant published literature concerning the neurobehavioral
             effects of developmental exposure of vertebrates to
             neonicotinoids. METHODS: Using zebrafish, we investigated
             the neurobehavioral effects of developmental exposure to
             imidacloprid, a prototypic neonicotinoid pesticide. Nicotine
             was also administered for comparison. Zebrafish were exposed
             via immersion in aqueous solutions containing 45 μM or 60
             μM of imidacloprid or nicotine (or vehicle control) from 4h
             to 5d post fertilization. The functional effects of
             developmental exposure to both imidacloprid and nicotine
             were assessed in larvae using an activity assay and during
             adolescence and adulthood using a battery of neurobehavioral
             assays, including assessment of sensorimotor response and
             habituation in a tactile startle test, novel tank swimming,
             and shoaling behavior. RESULTS: In larvae, developmental
             imidacloprid exposure at both doses significantly decreased
             swimming activity. The 5D strains of zebrafish were more
             sensitive to both nicotine and imidacloprid than the AB*
             strain. In adolescent and adult fish, developmental exposure
             to imidacloprid significantly decreased novel tank
             exploration and increased sensorimotor response to startle
             stimuli. While nicotine did not affect novel tank swimming,
             it increased sensorimotor response to startle stimuli at the
             low dose. No effects of either compound were found on
             shoaling behavior or habituation to a startling stimulus.
             DISCUSSION: Early developmental exposure to imidacloprid has
             both early-life and persisting effects on neurobehavioral
             function in zebrafish. Its developmental neurotoxicity
             should be further investigated.},
   Doi = {10.1016/j.ntt.2015.04.006},
   Key = {fds274173}
}

@article{fds274166,
   Author = {Bailey, JM and Oliveri, AN and Zhang, C and Frazier, JM and Mackinnon,
             S and Cole, GJ and Levin, ED},
   Title = {Long-term behavioral impairment following acute embryonic
             ethanol exposure in zebrafish.},
   Journal = {Neurotoxicol Teratol},
   Volume = {48},
   Pages = {1-8},
   Year = {2015},
   Month = {March},
   ISSN = {0892-0362},
   url = {http://dx.doi.org/10.1016/j.ntt.2015.01.005},
   Abstract = {BACKGROUND: Developmental exposure to ethanol has long been
             known to cause persisting neurobehavioral impairment.
             However, the neural and behavioral mechanisms underlying
             these deficits and the importance of exposure timing are not
             well-characterized. Given the importance of timing and
             sequence in neurodevelopment it would be expected that
             alcohol intoxication at different developmental periods
             would result in distinct neurobehavioral consequences.
             METHODS: Zebrafish embryos were exposed to ethanol (0%, 1%,
             3%) at either 8-10 or 24-27 h post-fertilization (hpf) then
             reared to adolescence and evaluated on several behavioral
             endpoints. Habituation to a repeated environmental stimulus
             and overall sensorimotor function were assessed using a tap
             startle test; measurements of anxiety and exploration
             behavior were made following introduction to a novel tank;
             and spatial discrimination learning was assessed using
             aversive control in a three-chambered apparatus. Overt signs
             of dysmorphogenesis were also scored (i.e. craniofacial
             malformations, including eye diameter and midbrain-hindbrain
             boundary morphology). RESULTS: Ethanol treated fish were
             more active both at baseline and following a tap stimulus
             compared to the control fish and were hyperactive when
             placed in a novel tank. These effects were more prominent
             following exposure at 24-27 hpf than with the earlier
             exposure window, for both dose groups. Increases in physical
             malformation were only present in the 3% ethanol group; all
             malformed fish were excluded from behavioral testing.
             DISCUSSION: These results suggest specific domains of
             behavior are affected following ethanol exposure, with some
             but not all of the tests revealing significant impairment.
             The behavioral phenotypes following distinct exposure
             windows described here can be used to help link cellular and
             molecular mechanisms of developmental ethanol exposure to
             functional neurobehavioral effects.},
   Doi = {10.1016/j.ntt.2015.01.005},
   Key = {fds274166}
}

@article{fds274167,
   Author = {Hall, BJ and Slade, S and Wells, C and Rose, JE and Levin,
             ED},
   Title = {Bupropion-varenicline interactions and nicotine
             self-administration behavior in rats.},
   Journal = {Pharmacol Biochem Behav},
   Volume = {130},
   Pages = {84-89},
   Year = {2015},
   Month = {March},
   ISSN = {0091-3057},
   url = {http://dx.doi.org/10.1016/j.pbb.2015.01.009},
   Abstract = {Varenicline and bupropion each have been shown to
             significantly improve cessation of tobacco addiction in
             humans. They act through different mechanisms and the
             question about the potential added efficacy with their
             combined used has arisen. Preclinical animal models of
             nicotine addiction can help with the evaluation of this
             combined approach and what dose combinations of varenicline
             and bupropion may be useful for enhancing tobacco cessation.
             In this study, we investigated the interacting dose-effect
             functions of varenicline and bupropion in a rat model of
             nicotine self-administration. Young adult female
             Sprague-Dawley rats were allowed to self-administer nicotine
             in 1-h sessions under an FR1 reinforcement schedule.
             Varenicline (0.3, 1. 3 mg/kg) and bupropion (8.33, 25, 75
             mg/kg) were administered alone or together 15 min before
             each session. The vehicle saline was the control. Higher
             doses of each drug alone reduced nicotine
             self-administration compared to control with reductions of
             62% and 75% with 3 mg/kg varenicline and 75 mg/kg bupropion
             respectively. Lower dose varenicline which does not by
             itself reduce nicotine self-administration, significantly
             augmented bupropion effects. The 0.3 mg/kg varenicline dose
             combined with the 25 and 75 mg/kg bupropion doses caused
             greater reductions of nicotine self-administration than
             either dose of bupropion given alone. However, higher dose
             varenicline did not have this effect. Lower dose bupropion
             did not augment varenicline effects. Only the high bupropion
             dose significantly enhanced the varenicline effect.
             Likewise, combining 1 mg/kg varenicline with 75 mg/kg
             bupropion reduced self-administration to a greater extent
             than either dose alone. These results demonstrate that
             combination therapy with varenicline and bupropion may be
             more beneficial than monotherapy with either drug
             alone.},
   Doi = {10.1016/j.pbb.2015.01.009},
   Key = {fds274167}
}

@article{fds274165,
   Author = {Slotkin, TA and Skavicus, S and Levin, ED and Seidler,
             FJ},
   Title = {Prenatal nicotine changes the response to postnatal
             chlorpyrifos: Interactions targeting serotonergic synaptic
             function and cognition.},
   Journal = {Brain Res Bull},
   Volume = {111},
   Pages = {84-96},
   Year = {2015},
   Month = {February},
   ISSN = {0361-9230},
   url = {http://dx.doi.org/10.1016/j.brainresbull.2015.01.003},
   Abstract = {Nicotine and chlorpyrifos are developmental neurotoxicants
             that target serotonin systems. We examined whether prenatal
             nicotine exposure alters the subsequent response to
             chlorpyrifos given postnatally. Pregnant rats received
             nicotine throughout gestation at 3mg/kg/day, a regimen
             designed to achieve plasma levels seen in smokers;
             chlorpyrifos was given to pups on postnatal days (PN) 1-4 at
             1mg/kg, just above the detection threshold for brain
             cholinesterase inhibition. We assessed long-term effects
             from adolescence (PN30) through full adulthood (PN150),
             measuring the expression of serotonin receptors and
             serotonin turnover (index of presynaptic impulse activity)
             in cerebrocortical brain regions encompassing the
             projections that are known targets for nicotine and
             chlorpyrifos. Nicotine or chlorpyrifos individually
             increased the expression of serotonin receptors, with
             greater effects on males than on females and with distinct
             temporal and regional patterns indicative of adaptive
             synaptic changes rather than simply an extension of initial
             injury. This interpretation was confirmed by our finding an
             increase in serotonin turnover, connoting presynaptic
             serotonergic hyperactivity. Animals receiving the combined
             treatment showed a reduction in these adaptive effects on
             receptor binding and turnover relative to the individual
             agents, or even an effect in the opposite direction;
             further, normal sex differences in serotonin receptor
             concentrations were dissipated or reversed, an effect that
             was confirmed by behavioral evaluations in the Novel
             Objection Recognition Test. In addition to the known
             liabilities associated with maternal smoking during
             pregnancy, our results point to additional costs in the form
             of heightened vulnerability to neurotoxic chemicals
             encountered later in life.},
   Doi = {10.1016/j.brainresbull.2015.01.003},
   Key = {fds274165}
}

@article{fds330185,
   Author = {Rezvani, AH and Levin, ED and Arolfo, MP and Wells, C and Graupe, M and Diamond, I},
   Title = {Inhibition of aldehyde dehydrogenase-2 (ALDH-2) suppresses
             nicotine self-administration in rats},
   Journal = {Journal of Drug and Alcohol Research},
   Volume = {4},
   Pages = {1-6},
   Publisher = {Ashdin Publishing},
   Year = {2015},
   Month = {January},
   url = {http://dx.doi.org/10.4303/jdar/235940},
   Abstract = {© 2015 Amir H. Rezvani et al. Introduction. Aldehyde
             dehydrogenase-2 (ALDH-2) inhibitors have been shown to
             reduce cocaine and alcohol intake in rats. The mechanism of
             action appears to be due to inhibition of drug-induced
             dopamine (DA) production in the ventral tegmental area (VTA)
             and DA release in the nucleus accumbens. The purpose of this
             study was to explore the potential of a selective ALDH-2
             inhibitor to reduce self-administration of nicotine.
             Materials and methods. Adult male rats were trained to
             self-administer nicotine intravenously. After acquiring a
             stable baseline for nicotine intake, rats were given one of
             the three oral gavage doses (5, 10 or 30mg eq/kg, calculated
             based on parent drug) of the prodrug GS-6637 of an ALDH-2
             inhibitor or vehicle one hour before a nicotine
             self-administration session. Results. Our data showed that
             acute administration of GS-6637 at 10 mg eq/kg and 30mg
             eq/kg significantly reduced nicotine self-administration.
             Similarly, subchronic administration of GS-6637 for seven
             days significantly reduced nicotine self-administration at
             10mg eq/kg and 30 mg eq/kg without inducing tolerance. In
             order to compare GS-6637 with varenicline, rats were given
             single doses of varenicline at 1.6, 3.2, and 6.4 mg/kg.
             Consistent with previous reports, significant inhibitions of
             nicotine self-administration was observed at the 3.2mg/kg
             and 6.4mg/kg doses but less than observed with GS-6637.
             Discussion and conclusions. Our data suggest that selective
             ALDH-2 inhibition appears to have therapeutic potentials as
             novel therapy for smoking cessation.},
   Doi = {10.4303/jdar/235940},
   Key = {fds330185}
}

@article{fds274168,
   Author = {Levin, ED and Hall, BJ and Rezvani, AH},
   Title = {Heterogeneity across brain regions and neurotransmitter
             interactions with nicotinic effects on memory
             function.},
   Journal = {Current Topics in Behavioral Neurosciences},
   Volume = {23},
   Pages = {87-101},
   Year = {2015},
   ISSN = {1866-3370},
   url = {http://dx.doi.org/10.1007/978-3-319-13665-3_4},
   Abstract = {Nicotinic acetylcholine receptors have been shown in many
             studies to be critically involved in memory function. The
             precise roles these receptors play depend on the receptor
             subtype, their anatomic localization, their interactions
             with other parts of the neural systems underlying cognition
             and the particular domain of cognitive function. Nicotinic
             agonists can significantly improve learning, memory, and
             attention. Nicotinic receptors in the hippocampus are
             innervated by cholinergic projections from the medial septum
             and diagonal band. Local infusions of either α7 or α4β2
             nicotinic antagonists into either the dorsal or ventral
             hippocampus produce amnestic effects in rats navigating
             about a radial arm maze. There is cholinergic innervation of
             nicotinic receptors in other components of the limbic system
             as well. In the basolateral amygdala and the anterior
             thalamus, similar amnestic effects of nicotinic α7 and
             α4β2 antagonists are seen. Interestingly, there are no
             additive amnestic effects observed in these limbic areas
             when α7 and α4β2 receptor antagonists are combined. The
             particular expression patterns of α7 and α4β2 nicotinic
             receptors in these limbic and cortical areas may explain
             this nonadditivity, but further research is needed to
             determine the specific cause of this phenomenon. Nicotinic
             receptor mechanisms in the limbic system play an important
             role in cognitive impairment for a variety of neurological
             disorders, including Alzheimer's disease and schizophrenia.
             Alzheimer's disease results in a dramatic decrease in
             hippocampal nicotinic receptor density, affecting α4β2
             receptor expression most prominently. In schizophrenia,
             there are anomalies in α7 nicotinic receptor expression,
             which seem to be crucial for the cognitive impairment of the
             disorder. Chronic nicotine exposure, such as seen with
             tobacco use, results in an increase in nicotinic receptor
             density in the limbic system. This effect appears to be
             related to the desensitization of nicotinic receptors seen
             after agonist application. Open questions remain concerning
             the role of desensitization versus activation of nicotinic
             receptors in cognitive improvement.},
   Doi = {10.1007/978-3-319-13665-3_4},
   Key = {fds274168}
}

@article{fds274181,
   Author = {Burke, DA and Heshmati, P and Kholdebarin, E and Levin,
             ED},
   Title = {Decreasing nicotinic receptor activity and the spatial
             learning impairment caused by the NMDA glutamate antagonist
             dizocilpine in rats.},
   Journal = {Eur J Pharmacol},
   Volume = {741},
   Pages = {132-139},
   Year = {2014},
   Month = {October},
   ISSN = {0014-2999},
   url = {http://dx.doi.org/10.1016/j.ejphar.2014.07.030},
   Abstract = {Nicotinic systems have been shown by a variety of studies to
             be involved in cognitive function. Nicotinic receptors have
             an inherent property to become desensitized after
             activation. The relative role of nicotinic receptor
             activation vs. net receptor inactivation by desensitization
             in the cognitive effects of nicotinic drugs remains to be
             fully understood. In these studies, we tested the effects of
             the α7 nicotinic receptor antagonist methyllycaconitine
             (MLA), the α4β2 nicotinic receptor antagonist
             dihydro-β-erythroidine (DHβE), the nonspecific nicotinic
             channel blocker mecamylamine and the α4β2 nicotinic
             receptor desensitizing agent sazetidine-A on learning in a
             repeated acquisition test. Adult female Sprague-Dawley rats
             were trained on a repeated acquisition learning procedure in
             an 8-arm radial maze. MLA (1-4mg/kg), DHβE (1-4mg/kg),
             mecamylamine (0.125-0.5mg/kg) or sazetidine-A (1 and 3mg/kg)
             were administered in four different studies either alone or
             together with the NMDA glutamate antagonist dizocilpine
             (0.05 and 0.10mg/kg). MLA significantly counteracted the
             learning impairment caused by dizocilpine. The overall
             choice accuracy impairment caused by dizocilpine was
             significantly attenuated by co-administration of DHβE. Low
             doses of the non-specific nicotinic antagonist mecamylamine
             also reduced dizocilpine-induced repeated acquisition
             impairment. Sazetidine-A reversed the accuracy impairment
             caused by dizocilpine. These studies provide evidence that a
             net decrease in nicotinic receptor activity can improve
             learning by attenuating learning impairment induced by NMDA
             glutamate blockade. This adds to evidence in cognitive tests
             that nicotinic antagonists can improve cognitive function.
             Further research characterizing the efficacy and mechanisms
             underlying nicotinic antagonist and desensitization induced
             cognitive improvement is warranted.},
   Doi = {10.1016/j.ejphar.2014.07.030},
   Key = {fds274181}
}

@article{fds274182,
   Author = {Cousins, V and Rose, JE and Levin, ED},
   Title = {IV nicotine self-administration in rats using a consummatory
             operant licking response: sensitivity to serotonergic,
             glutaminergic and histaminergic drugs.},
   Journal = {Prog Neuropsychopharmacol Biol Psychiatry},
   Volume = {54},
   Pages = {200-205},
   Year = {2014},
   Month = {October},
   ISSN = {0278-5846},
   url = {http://dx.doi.org/10.1016/j.pnpbp.2014.06.004},
   Abstract = {Tobacco smoking is characterized by repeated
             self-administration of nicotine by placing the cigarette in
             the mouth. The repeated hand-to-mouth self-administration is
             essentially a consummatory act. We recently developed a
             paradigm in which rats lick one of two spouts to trigger
             intravenous (IV) delivery of nicotine, which combines a
             consummatory act with rapid delivery of nicotine to model
             the act of tobacco smoking. We have found that rats will
             lick hundreds of times per nicotine infusion. In the current
             study, using the operant licking nicotine
             self-administration model with young adult Sprague-Dawley
             rats (0.03mg/kg/infusion of nicotine), we tested the effect
             of antagonists of H1 histamine receptors pyrilamine,
             serotonin (5HT) type 2 receptors ketanserin and
             N-methyl-d-aspartate (NMDA) glutamate receptors with
             d-cycloserine as well as an agonist of 5HT2c receptors
             lorcaserin, in dose ranges that we have found in previous
             studies to significantly reduce IV nicotine
             self-administration with the operant lever press operand.
             The H1 antagonist pyrilamine significantly reduced operant
             licking for nicotine self-administration. Pyrilamine caused
             significant reductions in the operant licking paradigm at
             lower doses (10 and 20mg/kg) than those we previously
             observed to affect responding in the operant lever press
             paradigm. In contrast, the 5HT2A and C antagonist ketanserin
             did not show an effect of reducing nicotine
             self-administration in the same dose range we had found in a
             previous study to significantly reduce operant lever press
             nicotine self-administration. The 5HT2C agonist lorcaserin
             significantly decreased nicotine self-administration in the
             licking paradigm at the same dose threshold as with lever
             press responding. The NMDA glutamate partial agonist
             d-cycloserine did not produce any change in nicotine
             self-administration with the licking operand, in contrast to
             its effect on the classic lever-pressing task. The rat model
             incorporating consummatory aspects of tobacco addiction can
             provide distinct and potentially more relevant information
             concerning possible new avenues of treatment to combat
             tobacco addiction.},
   Doi = {10.1016/j.pnpbp.2014.06.004},
   Key = {fds274182}
}

@article{fds274179,
   Author = {Rezvani, AH and Cauley, MC and Levin, ED},
   Title = {Lorcaserin, a selective 5-HT(2C) receptor agonist, decreases
             alcohol intake in female alcohol preferring
             rats.},
   Journal = {Pharmacol Biochem Behav},
   Volume = {125},
   Pages = {8-14},
   Year = {2014},
   Month = {October},
   ISSN = {0091-3057},
   url = {http://dx.doi.org/10.1016/j.pbb.2014.07.017},
   Abstract = {Serotonergic systems in the brain have been found to be
             important in the addiction to alcohol. The purpose of this
             study was to evaluate the efficacy of a novel 5-HT2c
             receptor agonist, lorcaserin for reducing alcohol
             consumption in alcohol-preferring (P) rats. Adult female
             rats were allowed to drink water or alcohol (12%, v/v) using
             a standard two-bottle choice procedure. Once stable
             baselines were established, the acute (0, 0.3125, 0.625 and
             1.25 mg/kg, s.c.), and chronic (0, 0.625 mg/kg, sc for 10
             days) effects of lorcaserin on alcohol intake and preference
             were assessed at different time points. In a separate
             experiment, the effects of lorcaserin on locomotor activity
             were determined. Our results show that both 0.625 and 1.25
             mg/kg lorcaserin significantly reduced alcohol intake at 2,
             4 and 6 h. after the drug administration. The chronic
             administration of 0.625 mg/kg lorcaserin significantly
             reduced alcohol intake up to 6h every day after the
             injection and there was no sign of diminished efficacy of
             the drug during 10-day treatment. To determine the effects
             of lorcaserin on sucrose intake, rats were put on a
             two-bottle choice of water vs a solution of 7% sucrose. The
             high dose of lorcaserin (1.25 mg/kg, s.c.) reduced sucrose
             intake only for up to 2 h. When tested for locomotor
             activity, lorcaserin injected 20 min before testing
             significantly reduced locomotor activity at all doses.
             However, when it was injected 5.5h before the start of the
             1-h session, neither dose had a significant effect on
             locomotor activity. These results show the efficacy of
             lorcaserin in reducing alcohol intake without a significant
             effect on water intake and locomotion suggesting the
             involvement of 5-HT2c receptors in alcohol seeking behavior.
             Further research is warranted to determine the possible
             efficacy of lorcaserin or similar drugs as treatments for
             the treatment of alcoholism.},
   Doi = {10.1016/j.pbb.2014.07.017},
   Key = {fds274179}
}

@article{fds274180,
   Author = {Levin, ED and Hao, I and Burke, DA and Cauley, M and Hall, BJ and Rezvani,
             AH},
   Title = {Effects of tobacco smoke constituents, anabasine and
             anatabine, on memory and attention in female
             rats.},
   Journal = {J Psychopharmacol},
   Volume = {28},
   Number = {10},
   Pages = {915-922},
   Year = {2014},
   Month = {October},
   ISSN = {0269-8811},
   url = {http://dx.doi.org/10.1177/0269881114543721},
   Abstract = {Nicotine has been well characterized to improve memory and
             attention. Nicotine is the primary, but not only neuroactive
             compound in tobacco. Other tobacco constituents such as
             anabasine and anatabine also have agonist actions on
             nicotinic receptors. The current study investigated the
             effects of anabasine and anatabine on memory and attention.
             Adult female Sprague-Dawley rats were trained on a win-shift
             spatial working and reference memory task in the 16-arm
             radial maze or a visual signal detection operant task to
             test attention. Acute dose-effect functions of anabasine and
             anatabine over two orders of magnitude were evaluated for
             both tasks. In the radial-arm maze memory test, anabasine
             but not anatabine significantly reduced the memory
             impairment caused by the NMDA antagonist dizocilpine
             (MK-801). In the signal detection attentional task,
             anatabine but not anabasine significantly attenuated the
             attentional impairment caused by dizocilpine. These studies
             show that non-nicotine nicotinic agonists in tobacco,
             similar to nicotine, can significantly improve memory and
             attentional function. Both anabasine and anatabine produced
             cognitive improvement, but their effectiveness differed with
             regard to memory and attention. Follow-up studies with
             anabasine and anatabine are called for to determine their
             efficacy as therapeutics for memory and attentional
             dysfunction.},
   Doi = {10.1177/0269881114543721},
   Key = {fds274180}
}

@article{fds274183,
   Author = {Slotkin, TA and Card, J and Stadler, A and Levin, ED and Seidler,
             FJ},
   Title = {Effects of tobacco smoke on PC12 cell neurodifferentiation
             are distinct from those of nicotine or benzo[a]pyrene.},
   Journal = {Neurotoxicol Teratol},
   Volume = {43},
   Pages = {19-24},
   Year = {2014},
   Month = {May},
   ISSN = {0892-0362},
   url = {http://dx.doi.org/10.1016/j.ntt.2014.03.002},
   Abstract = {Although nicotine accounts for a great deal of the
             neurodevelopmental damage associated with maternal smoking
             or second-hand exposure, tobacco smoke contains thousands of
             potentially neurotoxic compounds. We used PC12 cells, a
             standard in vitro model of neurodifferentiation, to compare
             tobacco smoke extract (TSE) to nicotine, matching TSE
             exposure (with its inherent nicotine content) to parallel
             concentrations of nicotine, or to benzo[a]pyrene, a tobacco
             combustion product. TSE promoted the transition from cell
             replication to differentiation, resulting in fewer, but
             larger cells with greater neurite extension. TSE also biased
             differentiation into the dopaminergic versus the cholinergic
             phenotype, evidenced by an increase in tyrosine hydroxylase
             activity but not choline acetyltransferase. Nicotine
             likewise promoted differentiation at the expense of cell
             numbers, but its effect on growth and neurite extension was
             smaller than that of TSE; furthermore, nicotine did not
             promote the dopaminergic phenotype. Benzo[a]pyrene had
             effects opposite to those of TSE, retarding
             neurodifferentiation, which resulted in higher cell numbers,
             smaller cells, reduced neurite information, and impaired
             emergence of both dopaminergic and cholinergic phenotypes.
             Our studies show that the complex mixture of compounds in
             tobacco smoke exerts direct effects on neural cell
             replication and differentiation that resemble those of
             nicotine in some ways but not others, and most importantly,
             that are greater in magnitude than can be accounted for from
             just the nicotine content of TSE. Thus, fetal tobacco smoke
             exposure, including lower levels associated with second-hand
             smoke, could be more injurious than would be anticipated
             from measured levels of nicotine or its metabolites.},
   Doi = {10.1016/j.ntt.2014.03.002},
   Key = {fds274183}
}

@article{fds274184,
   Author = {Hall, BJ and Wells, C and Allenby, C and Lin, MY and Hao, I and Marshall,
             L and Rose, JE and Levin, ED},
   Title = {Differential effects of non-nicotine tobacco constituent
             compounds on nicotine self-administration in
             rats.},
   Journal = {Pharmacol Biochem Behav},
   Volume = {120},
   Pages = {103-108},
   Year = {2014},
   Month = {May},
   ISSN = {0091-3057},
   url = {http://dx.doi.org/10.1016/j.pbb.2014.02.011},
   Abstract = {Tobacco smoking has been shown to be quite addictive in
             people. However, nicotine itself is a weak reinforcer
             compared to other commonly abused drugs, leading speculation
             that other factors contribute to the high prevalence of
             tobacco addiction in the human population. In addition to
             nicotine, there are over 5000 chemical compounds that have
             been identified in tobacco smoke, and more work is needed to
             ascertain their potential contributions to tobacco's highly
             addictive properties, or as potential candidates for smoking
             cessation treatment. In this study, we examined seven
             non-nicotine tobacco constituent compounds (anabasine,
             anatabine, nornicotine, myosmine, harmane, norharmane, and
             tyramine) for their effects on nicotine self-administration
             behavior in rats. Young adult female Sprague-Dawley rats
             were allowed to self-administer nicotine (0.03 mg/kg/50 μl
             infusion) under a fixed ratio-1 schedule of reinforcement.
             Each self-administration session lasted 45 min. Doses of
             each tobacco constituent compound were administered
             subcutaneously 10 min prior to the start of each session in
             a repeated measures, counterbalanced order two times.
             Anabasine displayed a biphasic dose-effect function.
             Pretreatment with 0.02 mg/kg anabasine resulted in a 25%
             increase in nicotine self-administration, while 2.0mg/kg of
             anabasine reduced nicotine infusions per session by over
             50%. Pretreatment with 2.0mg/kg anatabine also significantly
             reduced nicotine self-administration by nearly half. These
             results suggest that some non-nicotine tobacco constituents
             may enhance or reduce nicotine's reinforcing properties.
             Also, depending upon the appropriate dose, some of these
             compounds may also serve as potential smoking cessation
             agents.},
   Doi = {10.1016/j.pbb.2014.02.011},
   Key = {fds274184}
}

@article{fds274186,
   Author = {Levin, ED},
   Title = {Nicotinic attention-deficit/hyperactivity disorder
             treatment.},
   Journal = {Biol Psychiatry},
   Volume = {75},
   Number = {3},
   Pages = {174},
   Year = {2014},
   Month = {February},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/24370349},
   Doi = {10.1016/j.biopsych.2013.11.024},
   Key = {fds274186}
}

@article{fds274193,
   Author = {Larrauri, JA and Kelley, LD and Jenkins, MR and Westman, EC and Schmajuk, NA and Rosenthal, MZ and Levin, ED},
   Title = {Meclizine enhancement of sensorimotor gating in healthy male
             subjects with high startle responses and low prepulse
             inhibition.},
   Journal = {Neuropsychopharmacology},
   Volume = {39},
   Number = {3},
   Pages = {651-659},
   Year = {2014},
   Month = {February},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/24045586},
   Abstract = {Histamine H1 receptor systems have been shown in animal
             studies to have important roles in the reversal of
             sensorimotor gating deficits, as measured by prepulse
             inhibition (PPI). H1-antagonist treatment attenuates the PPI
             impairments caused by either blockade of NMDA glutamate
             receptors or facilitation of dopamine transmission. The
             current experiment brought the investigation of H1 effects
             on sensorimotor gating to human studies. The effects of the
             histamine H1 antagonist meclizine on the startle response
             and PPI were investigated in healthy male subjects with high
             baseline startle responses and low PPI levels. Meclizine was
             administered to participants (n=24) using a within-subjects
             design with each participant receiving 0, 12.5, and 25 mg
             of meclizine in a counterbalanced order. Startle response,
             PPI, heart rate response, galvanic skin response, and
             changes in self-report ratings of alertness levels and
             affective states (arousal and valence) were assessed. When
             compared with the control (placebo) condition, the two doses
             of meclizine analyzed (12.5 and 25 mg) produced
             significant increases in PPI without affecting the magnitude
             of the startle response or other physiological variables.
             Meclizine also caused a significant increase in overall
             self-reported arousal levels, which was not correlated with
             the observed increase in PPI. These results are in agreement
             with previous reports in the animal literature and suggest
             that H1 antagonists may have beneficial effects in the
             treatment of subjects with compromised sensorimotor gating
             and enhanced motor responses to sensory stimuli.},
   Doi = {10.1038/npp.2013.248},
   Key = {fds274193}
}

@article{fds274190,
   Author = {Levin, ED and Cauley, M and Johnson, JE and Cooper, EM and Stapleton,
             HM and Ferguson, PL and Seidler, FJ and Slotkin, TA},
   Title = {Prenatal dexamethasone augments the neurobehavioral
             teratology of chlorpyrifos: significance for maternal stress
             and preterm labor.},
   Journal = {Neurotoxicol Teratol},
   Volume = {41},
   Pages = {35-42},
   Year = {2014},
   Month = {January},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/24177596},
   Abstract = {Glucocorticoids are the consensus treatment given in preterm
             labor and are also elevated by maternal stress;
             organophosphate exposures are virtually ubiquitous, so human
             developmental coexposures to these two agents are common.
             This study explores how prenatal dexamethasone exposure
             modifies the neurobehavioral teratology of chlorpyrifos, one
             of the most widely used organophosphates. We administered
             dexamethasone to pregnant rats on gestational days 17-19 at
             a standard therapeutic dose (0.2 mg/kg); offspring were then
             given chlorpyrifos on postnatal days 1-4, at a dose (1
             mg/kg) that produces barely-detectable (<10%) inhibition of
             brain cholinesterase activity. Dexamethasone did not alter
             brain chlorpyrifos concentrations, nor did either agent
             alone or in combination affect brain thyroxine levels.
             Assessments were carried out from adolescence through
             adulthood encompassing T-maze alternation, Figure 8 maze
             (locomotor activity, habituation), novelty-suppressed
             feeding and novel object recognition tests. For behaviors
             where chlorpyrifos or dexamethasone individually had small
             effects, the dual exposure produced larger, significant
             effects that reflected additivity (locomotor activity,
             novelty-suppressed feeding, novel object recognition). Where
             the individual effects were in opposite directions or were
             restricted to only one agent, we found enhancement of
             chlorpyrifos' effects by prenatal dexamethasone
             (habituation). Finally, for behaviors where controls
             displayed a normal sex difference in performance, the
             combined treatment either eliminated or reversed the
             difference (locomotor activity, novel object recognition).
             Combined exposure to dexamethasone and chlorpyrifos results
             in a worsened neurobehavioral outcome, providing a
             proof-of-principle that prenatal glucocorticoids can create
             a subpopulation with enhanced vulnerability to environmental
             toxicants.},
   Doi = {10.1016/j.ntt.2013.10.004},
   Key = {fds274190}
}

@article{fds274189,
   Author = {Yenugonda, VM and Xiao, Y and Levin, ED and Rezvani, AH and Tran, T and Al-Muhtasib, N and Sahibzada, N and Xie, T and Wells, C and Slade, S and Johnson, JE and Dakshanamurthy, S and Kong, H-S and Tomita, Y and Liu,
             Y and Paige, M and Kellar, KJ and Brown, ML},
   Title = {Design, synthesis and discovery of picomolar selective
             α4β2 nicotinic acetylcholine receptor ligands.},
   Journal = {Journal of Medicinal Chemistry},
   Volume = {56},
   Number = {21},
   Pages = {8404-8421},
   Year = {2013},
   Month = {November},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/24047231},
   Abstract = {Developing novel and selective compounds that desensitize
             α4β2 nicotinic acetylcholine receptors (nAChRs) could
             provide new effective treatments for nicotine addiction, as
             well as other disorders. Here we report a new class of nAChR
             ligands that display high selectivity and picomolar binding
             affinity for α4β2 nicotinic receptors. The novel compounds
             have Ki values in the range of 0.031-0.26 nM and properties
             that should make them good candidates as drugs acting in the
             CNS. The selected lead compound 1 (VMY-2-95) binds with high
             affinity and potently desensitizes α4β2 nAChRs. At a dose
             of 3 mg/kg, compound 1 significantly reduced rat nicotine
             self-administration. The overall results support further
             characterizations of compound 1 and its analogues in
             preclinical models of nicotine addiction and perhaps other
             disorders involving nAChRs.},
   Doi = {10.1021/jm4008455},
   Key = {fds274189}
}

@article{fds274195,
   Author = {Kutlu, MG and Burke, D and Slade, S and Hall, BJ and Rose, JE and Levin,
             ED},
   Title = {Role of insular cortex D₁ and D₂ dopamine receptors in
             nicotine self-administration in rats.},
   Journal = {Behav Brain Res},
   Volume = {256},
   Pages = {273-278},
   Year = {2013},
   Month = {November},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/23948214},
   Abstract = {The insular cortex has been associated with the processing
             of rewarding stimuli and with the neural bases of drug
             addiction. Ischemic damage to the insula has been associated
             with decreased desire to smoke cigarettes. Which component
             of insular function is involved in the neural basis of
             cigarette smoking is not clear. Dopamine systems are crucial
             for the reinforcing value of addictive drugs. The DA
             projection from the ventral tegmental area to the nucleus
             accumbens (NAc) has been shown to be a vital pathway for the
             primary reinforcement caused by taking a variety of abused
             drugs. In the current set of studies, the roles of D₁ and
             D₂ receptors in the insular cortex in the
             self-administration of nicotine by rats were assessed. Adult
             female Sprague-Dawley rats were fitted with jugular
             catheters and given access to self-administer nicotine.
             Bilateral local infusion cannulae were implanted into the
             agranular insular cortex to locally administer D₁ and D₂
             antagonists (SCH-23390 and haloperidol). Acute local
             infusions of the D₁ antagonist SCH-23390 into the insula
             (1-2 μg/side) significantly decreased nicotine
             self-administration by more than 50%. Repeated infusions of
             SCH-23390 into the agranular insula caused continuing
             decreases in nicotine self-administration without signs of
             tolerance. In contrast, local infusions of the D₂
             antagonist haloperidol 0.5-2 μg/side did not have any
             discernable effect on nicotine self-administration. These
             studies show the importance of DA D₁ systems in the insula
             for nicotine reward.},
   Doi = {10.1016/j.bbr.2013.08.005},
   Key = {fds274195}
}

@article{fds274194,
   Author = {Levin, ED and Sexton, HG and Gordon, K and Gordon, CJ and Xiao, Y and Kellar, KJ and Yenugonda, VM and Liu, Y and White, MP and Paige, M and Brown, ML and Rezvani, AH},
   Title = {Effects of the sazetidine-a family of compounds on the body
             temperature in wildtype, nicotinic receptor β2-/- and
             α7-/- mice.},
   Journal = {Eur J Pharmacol},
   Volume = {718},
   Number = {1-3},
   Pages = {167-172},
   Year = {2013},
   Month = {October},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/24036108},
   Abstract = {Nicotine elicits hypothermic responses in rodents. This
             effect appears to be related to nicotinic receptor
             desensitization because sazetidine-A, an α4β2 nicotinic
             receptor desensitizing agent, produces marked hypothermia
             and potentiates nicotine-induced hypothermia in mice. To
             determine the specificity of sazetidine-A induced
             hypothermia to β2 subunit-containing nicotinic receptors,
             we tested its efficacy in β2 knockout (β2(-/-)) mice.
             These effects were compared with wildtype (WT) and α7
             knockout (α7(-/-)) mice. Confirming our earlier results,
             sazetidine-A elicited a pronounced and long-lasting
             hypothermia in WT mice. In comparison, sazetidine-A induced
             a much attenuated and shorter hypothermic response in
             β2(-/-) mice. This indicates that the greater proportion of
             sazetidine-A induced hypothermia is mediated via actions on
             β2-containing nicotinic receptors, while a smaller
             component of hypothermia induced by sazetidine-A is mediated
             by non-β2 receptors. Similar to WT mice, α7(-/-) mice
             showed the full extent of the sazetidine-A effect,
             suggesting that the hypothermia produced by sazetidine-A did
             not depend on actions on α7 nicotinic receptor subtype.
             Three other novel nicotinic receptor desensitizing agents
             derived from sazetidine-A, triazetidine-O, VMY-2-95 and
             YL-1-127 also produced hypothermia in WT and α7(-/-) mice.
             Furthermore, unlike sazetidine-A, triazetidine-O and
             YL-1-127 did not show any hint of a hypothermic effect in
             β2(-/-) mice. VMY-2-95 like sazetidine-A did show a
             residual hypothermic effect in the β2(-/-) mice. These
             studies show that the hypothermic effects of sazetidine-A
             and the related compound VMY-2-95 are mainly mediated by
             nicotinic receptors containing β2 subunit, but that a small
             component of the effect is apparently mediated by non-β2
             containing receptors.},
   Doi = {10.1016/j.ejphar.2013.08.037},
   Key = {fds274194}
}

@article{fds274196,
   Author = {Levin, ED},
   Title = {Complex relationships of nicotinic receptor actions and
             cognitive functions.},
   Journal = {Biochem Pharmacol},
   Volume = {86},
   Number = {8},
   Pages = {1145-1152},
   Year = {2013},
   Month = {October},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/23928190},
   Abstract = {Nicotine has been shown in a variety of studies to improve
             cognitive function including learning, memory and attention.
             Nicotine both stimulates and desensitizes nicotinic
             receptors, thus acting both as an agonist and a net
             antagonist. The relative roles of these two actions for
             nicotine-induced cognitive improvement have not yet been
             fully determined. We and others have found that acute
             nicotinic antagonist treatment can improve learning and
             attention. Nicotine acts on a variety of nicotinic receptor
             subtypes. The relative role and interactions of neuronal
             nicotinic receptor subtypes for cognition also needs to be
             better characterized. Nicotine acts on nicotinic receptors
             in a wide variety of brain areas. The role of some of these
             areas such as the hippocampus has been relatively well
             studied but other areas like the thalamus, which has the
             densest nicotinic receptor concentration are still only
             partially characterized. In a series of studies we
             characterized nicotinic receptor actions, anatomic
             localization and circuit interactions, which are critical to
             nicotine effects on the cognitive functions of learning,
             memory and attention. The relative role of increases and
             decreases in nicotinic receptor activation by nicotine were
             determined in regionally specific studies of the
             hippocampus, the amygdala, the frontal cortex and the
             mediodorsal thalamic nucleus with local infusions of
             antagonists of nicotinic receptor subtypes (α7 and α4β2).
             The understanding of the functional neural bases of
             cognitive function is fundamental to the more effective
             development of nicotinic drugs for treating cognitive
             dysfunction.},
   Doi = {10.1016/j.bcp.2013.07.021},
   Key = {fds274196}
}

@article{fds274198,
   Author = {Rezvani, AH and Sexton, HG and Johnson, J and Wells, C and Gordon, K and Levin, ED},
   Title = {Effects of caffeine on alcohol consumption and nicotine
             self-administration in rats.},
   Journal = {Alcohol Clin Exp Res},
   Volume = {37},
   Number = {9},
   Pages = {1609-1617},
   Year = {2013},
   Month = {September},
   ISSN = {0145-6008},
   url = {http://dx.doi.org/10.1111/acer.12127},
   Abstract = {BACKGROUND: Caffeine, alcohol, and nicotine are 3 of the
             most widespread self-administered psychoactive substances,
             which are known to be extensively co-administered. However,
             little is known about the degree to which they may mutually
             potentiate each other's consumption. METHODS: In the current
             set of studies, we examined in rats the effect of caffeine
             administration on alcohol drinking and intravenous (i.v.)
             self-administration of nicotine. In male alcohol-preferring
             (P) rats, caffeine (5, 10, and 20 mg/kg) or the saline
             vehicle was administered acutely either by subcutaneous
             (S.C.) injection or orally (PO) by gavage. In a chronic
             study, the effect of PO caffeine (5 and 20 mg/kg) on alcohol
             intake over a 10-day period was tested. In another
             experiment, the effect of acute PO administration of
             caffeine (20 mg/kg) or saline on saccharin intake (0.2%
             solution) was determined in P rats. Effects of 20 mg/kg
             caffeine on motor activity were also determined in P rats.
             Finally, the effects of acute PO caffeine administration on
             nicotine self-administration in Sprague-Dawley rats were
             also determined. RESULTS: Both routes of administration of
             caffeine, S.C. and PO, caused a significant dose-related
             decrease in alcohol intake and preference during free access
             to alcohol and after 4-day deprivation of alcohol. However,
             the low dose of 5 mg/kg caffeine increased alcohol intake.
             Acute PO caffeine also reduced saccharin intake. Acute
             systemic administration of 20 mg/kg caffeine did not exert a
             significant effect on motor activity. In Sprague-Dawley rats
             trained to self-administer i.v. nicotine, acute PO
             administration of caffeine significantly increased
             self-administration of nicotine in a dose-related manner.
             CONCLUSIONS: These results suggest that adenosine receptor
             systems may play a role in both alcohol and nicotine intake
             and deserve further study regarding these
             addictions.},
   Doi = {10.1111/acer.12127},
   Key = {fds274198}
}

@article{fds274199,
   Author = {Liu, Y and Richardson, J and Tran, T and Al-Muhtasib, N and Xie, T and Yenugonda, VM and Sexton, HG and Rezvani, AH and Levin, ED and Sahibzada, N and Kellar, KJ and Brown, ML and Xiao, Y and Paige,
             M},
   Title = {Chemistry and pharmacological studies of
             3-alkoxy-2,5-disubstituted-pyridinyl compounds as novel
             selective α4β2 nicotinic acetylcholine receptor ligands
             that reduce alcohol intake in rats.},
   Journal = {Journal of Medicinal Chemistry},
   Volume = {56},
   Number = {7},
   Pages = {3000-3011},
   Year = {2013},
   Month = {April},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/23540678},
   Abstract = {Neuronal acetylcholine receptors mediate the addictive
             effects of nicotine and may also be involved in alcohol
             addiction. Varenicline, an approved smoking cessation
             medication, showed clear efficacy in reducing alcohol
             consumption in heavy-drinking smokers. More recently,
             sazetidine-A, which selectively desensitizes α4β2
             nicotinic receptors, was shown to significantly reduce
             alcohol intake in a rat model. To develop novel therapeutics
             for treating alcohol use disorder, we designed and
             synthesized novel sazetidine-A analogues containing a methyl
             group at the 2-position of the pyridine ring. In vitro
             pharmacological studies revealed that some of the novel
             compounds showed overall pharmacological property profiles
             similar to that of sazetidine-A but exhibited reduced
             agonist activity across all nicotinic receptor subtypes
             tested. In rat studies, compound (S)-9 significantly reduced
             alcohol uptake. More importantly, preliminary results from
             studies in a ferret model indicate that these novel nAChR
             ligands have an improved adverse side-effect profile in
             comparison with that of varenicline.},
   Doi = {10.1021/jm4000374},
   Key = {fds274199}
}

@article{fds274200,
   Author = {Bailey, J and Oliveri, A and Levin, ED},
   Title = {Zebrafish model systems for developmental neurobehavioral
             toxicology.},
   Journal = {Birth Defects Res C Embryo Today},
   Volume = {99},
   Number = {1},
   Pages = {14-23},
   Year = {2013},
   Month = {March},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/23723169},
   Abstract = {Zebrafish offer many advantages that complement classic
             mammalian models for the study of normal development as well
             as for the teratogenic effects of exposure to hazardous
             compounds. The clear chorion and embryo of the zebrafish
             allow for continuous visualization of the anatomical changes
             associated with development, which, along with short
             maturation times and the capability of complex behavior,
             makes this model particularly useful for measuring changes
             to the developing nervous system. Moreover, the rich array
             of developmental, behavioral, and molecular benefits offered
             by the zebrafish have contributed to an increasing demand
             for the use of zebrafish in behavioral teratology. Essential
             for this endeavor has been the development of a battery of
             tests to evaluate a spectrum of behavior in zebrafish.
             Measures of sensorimotor plasticity, emotional function,
             cognition and social interaction have been used to
             characterize the persisting adverse effects of developmental
             exposure to a variety of chemicals including therapeutic
             drugs, drugs of abuse and environmental toxicants. In this
             review, we present and discuss such tests and data from a
             range of developmental neurobehavioral toxicology studies
             using zebrafish as a model. Zebrafish provide a key
             intermediate model between high throughput in vitro screens
             and the classic mammalian models as they have the
             accessibility of in vitro models and the complex functional
             capabilities of mammalian models.},
   Doi = {10.1002/bdrc.21027},
   Key = {fds274200}
}

@article{fds274311,
   Author = {Rezvani, AH and Cauley, M and Xiao, Y and Kellar, KJ and Levin,
             ED},
   Title = {Effects of chronic sazetidine-A, a selective α4β2 neuronal
             nicotinic acetylcholine receptors desensitizing agent on
             pharmacologically-induced impaired attention in
             rats.},
   Journal = {Psychopharmacology (Berl)},
   Volume = {226},
   Number = {1},
   Pages = {35-43},
   Year = {2013},
   Month = {March},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/23100170},
   Abstract = {RATIONALE: Nicotine and nicotinic agonists have been shown
             to improve attentional function. Nicotinic receptors are
             easily desensitized, and all nicotinic agonists are also
             desensitizing agents. Although both receptor activation and
             desensitization are components of the mechanism that
             mediates the overall effects of nicotinic agonists, it is
             not clear how each of the two opposed actions contributes to
             attentional improvements. Sazetidine-A has high binding
             affinity at α4β2 nicotinic receptors and causes a
             relatively brief activation followed by a long-lasting
             desensitization of the receptors. Acute administration of
             sazetidine-A has been shown to significantly improve
             attention by reversing impairments caused by the muscarinic
             cholinergic antagonist scopolamine and the NMDA glutamate
             antagonist dizocilpine. METHODS: In the current study, we
             tested the effects of chronic subcutaneous infusion of
             sazetidine-A (0, 2, or 6 mg/kg/day) on attention in
             Sprague-Dawley rats. Furthermore, we investigated the
             effects of chronic sazetidine-A treatment on attentional
             impairment induced by an acute administration of 0.02 mg/kg
             scopolamine. RESULTS: During the first week period, the
             6-mg/kg/day sazetidine-A dose significantly reversed the
             attentional impairment induced by scopolamine. During
             weeks 3 and 4, the scopolamine-induced impairment was no
             longer seen, but sazetidine-A (6 mg/kg/day) significantly
             improved attentional performance on its own. Chronic
             sazetidine-A also reduced response latency and response
             omissions. CONCLUSIONS: This study demonstrated that similar
             to its acute effects, chronic infusions of sazetidine-A
             improve attentional performance. The results indicate that
             the desensitization of α4β2 nicotinic receptors with some
             activation of these receptors may play an important role in
             improving effects of sazetidine-A on attention.},
   Doi = {10.1007/s00213-012-2895-6},
   Key = {fds274311}
}

@article{fds274203,
   Author = {Levin, ED and Cauley, M and Rezvani, AH},
   Title = {Improvement of attentional function with antagonism of
             nicotinic receptors in female rats.},
   Journal = {Eur J Pharmacol},
   Volume = {702},
   Number = {1-3},
   Pages = {269-274},
   Year = {2013},
   Month = {February},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/23399762},
   Abstract = {Nicotinic agonists have been shown in a variety of studies
             to improve cognitive function. Since nicotinic receptors are
             easily desensitized by agonists, it is not completely clear
             to what degree receptor desensitization or receptor
             activation are responsible for nicotinic agonist-induced
             cognitive improvement. In the current study, the effect of
             the neuronal nicotinic cholinergic α4β2 receptor
             antagonist dihydro-β-erythroidine (DHβE) and the α7
             nicotinic receptor antagonist methyllycaconitine (MLA) on
             attentional function was determined. Adult female
             Sprague-Dawley rats were trained on the visual signal
             detection task. They were required to discriminate whether
             or not a light signal occurred on a trial and respond with a
             lever press on one side after a signal and the opposite side
             after the absence of a signal in order to receive a food
             pellet reinforcer. Acute administration of the α4β2
             antagonist DHβE improved attentional function either alone
             or in reversing the attentional impairment caused by the
             NMDA glutamate antagonist dizocilpine (MK-801). Acute
             administration of MLA also significantly attenuated the
             dizocilpine-induced attentional impairment. In previous
             research we have shown that the α4β2 nicotinic
             desensitizing agent and partial agonist sazetidine-A also
             was effective in reversing dizocilpine-induced attentional
             impairments on the signal detection task and that low doses
             of the general nicotinic antagonist mecamylamine improved
             learning and memory. The current studies indicate that
             blockade of nicotinic receptors can effectively attenuate
             attentional impairments. Development of drugs that provide a
             net decrease in nicotinic receptor activity either through
             antagonism or desensitization could be worth exploring for
             beneficial effects for treating cognitive
             impairments.},
   Doi = {10.1016/j.ejphar.2013.01.056},
   Key = {fds274203}
}

@article{fds274204,
   Author = {Coppola, A and Wenner, BR and Ilkayeva, O and Stevens, RD and Maggioni,
             M and Slotkin, TA and Levin, ED and Newgard, CB},
   Title = {Branched-chain amino acids alter neurobehavioral function in
             rats.},
   Journal = {Am J Physiol Endocrinol Metab},
   Volume = {304},
   Number = {4},
   Pages = {E405-E413},
   Year = {2013},
   Month = {February},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/23249694},
   Abstract = {Recently, we have described a strong association of
             branched-chain amino acids (BCAA) and aromatic amino acids
             (AAA) with obesity and insulin resistance. In the current
             study, we have investigated the potential impact of BCAA on
             behavioral functions. We demonstrate that supplementation of
             either a high-sucrose or a high-fat diet with BCAA induces
             anxiety-like behavior in rats compared with control groups
             fed on unsupplemented diets. These behavioral changes are
             associated with a significant decrease in the concentration
             of tryptophan (Trp) in brain tissues and a consequent
             decrease in serotonin but no difference in indices of
             serotonin synaptic function. The anxiety-like behaviors and
             decreased levels of Trp in the brain of BCAA-fed rats were
             reversed by supplementation of Trp in the drinking water but
             not by administration of fluoxetine, a selective serotonin
             reuptake inhibitor, suggesting that the behavioral changes
             are independent of the serotonergic pathway of Trp
             metabolism. Instead, BCAA supplementation lowers the brain
             levels of another Trp-derived metabolite, kynurenic acid,
             and these levels are normalized by Trp supplementation. We
             conclude that supplementation of high-energy diets with BCAA
             causes neurobehavioral impairment. Since BCAA are elevated
             spontaneously in human obesity, our studies suggest a
             potential mechanism for explaining the strong association of
             obesity and mood disorders.},
   Doi = {10.1152/ajpendo.00373.2012},
   Key = {fds274204}
}

@article{fds274202,
   Author = {Behl, M and Rao, D and Aagaard, K and Davidson, TL and Levin, ED and Slotkin, TA and Srinivasan, S and Wallinga, D and White, MF and Walker,
             VR and Thayer, KA and Holloway, AC},
   Title = {Evaluation of the association between maternal smoking,
             childhood obesity, and metabolic disorders: a national
             toxicology program workshop review.},
   Journal = {Environ Health Perspect},
   Volume = {121},
   Number = {2},
   Pages = {170-180},
   Year = {2013},
   Month = {February},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/23232494},
   Abstract = {BACKGROUND: An emerging literature suggests that
             environmental chemicals may play a role in the development
             of childhood obesity and metabolic disorders, especially
             when exposure occurs early in life. OBJECTIVE: Here we
             assess the association between these health outcomes and
             exposure to maternal smoking during pregnancy as part of a
             broader effort to develop a research agenda to better
             understand the role of environmental chemicals as potential
             risk factors for obesity and metabolic disorders. METHODS:
             PubMed was searched up to 8 March 2012 for epidemiological
             and experimental animal studies related to maternal smoking
             or nicotine exposure during pregnancy and childhood obesity
             or metabolic disorders at any age. A total of 101 studies-83
             in humans and 18 in animals-were identified as the primary
             literature. DISCUSSION: Current epidemiological data support
             a positive association between maternal smoking and
             increased risk of obesity or overweight in offspring. The
             data strongly suggest a causal relation, although the
             possibility that the association is attributable to
             unmeasured residual confounding cannot be completely ruled
             out. This conclusion is supported by findings from
             laboratory animals exposed to nicotine during development.
             The existing literature on human exposures does not support
             an association between maternal smoking during pregnancy and
             type 1 diabetes in offspring. Too few human studies have
             assessed outcomes related to type 2 diabetes or metabolic
             syndrome to reach conclusions based on patterns of findings.
             There may be a number of mechanistic pathways important for
             the development of aberrant metabolic outcomes following
             perinatal exposure to cigarette smoke, which remain largely
             unexplored. CONCLUSIONS: From a toxicological perspective,
             the linkages between maternal smoking during pregnancy and
             childhood overweight/obesity provide proof-of-concept of how
             early-life exposure to an environmental toxicant can be a
             risk factor for childhood obesity.},
   Doi = {10.1289/ehp.1205404},
   Key = {fds274202}
}

@article{fds274201,
   Author = {Risher, M-L and Fleming, RL and Boutros, N and Semenova, S and Wilson,
             WA and Levin, ED and Markou, A and Swartzwelder, HS and Acheson,
             SK},
   Title = {Long-term effects of chronic intermittent ethanol exposure
             in adolescent and adult rats: radial-arm maze performance
             and operant food reinforced responding.},
   Journal = {Plos One},
   Volume = {8},
   Number = {5},
   Pages = {e62940},
   Year = {2013},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/23675442},
   Abstract = {BACKGROUND: Adolescence is not only a critical period of
             late-stage neurological development in humans, but is also a
             period in which ethanol consumption is often at its highest.
             Given the prevalence of ethanol use during this vulnerable
             developmental period we assessed the long-term effects of
             chronic intermittent ethanol (CIE) exposure during
             adolescence, compared to adulthood, on performance in the
             radial-arm maze (RAM) and operant food-reinforced responding
             in male rats. METHODOLOGY/PRINCIPAL FINDINGS: Male Sprague
             Dawley rats were exposed to CIE (or saline) and then allowed
             to recover. Animals were then trained in either the RAM task
             or an operant task using fixed- and progressive- ratio
             schedules. After baseline testing was completed all animals
             received an acute ethanol challenge while blood ethanol
             levels (BECs) were monitored in a subset of animals. CIE
             exposure during adolescence, but not adulthood decreased the
             amount of time that animals spent in the open portions of
             the RAM arms (reminiscent of deficits in risk-reward
             integration) and rendered animals more susceptible to the
             acute effects of an ethanol challenge on working memory
             tasks. The operant food reinforced task showed that these
             effects were not due to altered food motivation or to
             differential sensitivity to the nonspecific
             performance-disrupting effects of ethanol. However, CIE
             pre-treated animals had lower BEC levels than controls
             during the acute ethanol challenges indicating persistent
             pharmacokinetic tolerance to ethanol after the CIE
             treatment. There was little evidence of enduring effects of
             CIE alone on traditional measures of spatial and working
             memory. CONCLUSIONS/SIGNIFICANCE: These effects indicate
             that adolescence is a time of selective vulnerability to the
             long-term effects of repeated ethanol exposure on
             neurobehavioral function and acute ethanol sensitivity. The
             positive and negative findings reported here help to further
             define the nature and extent of the impairments observed
             after adolescent CIE and provide direction for future
             research.},
   Doi = {10.1371/journal.pone.0062940},
   Key = {fds274201}
}

@article{fds274319,
   Author = {Hussmann, GP and Turner, JR and Lomazzo, E and Venkatesh, R and Cousins,
             V and Xiao, Y and Yasuda, RP and Wolfe, BB and Perry, DC and Rezvani, AH and Levin, ED and Blendy, JA and Kellar, KJ},
   Title = {Chronic sazetidine-A at behaviorally active doses does not
             increase nicotinic cholinergic receptors in rodent
             brain.},
   Journal = {Journal of Pharmacology and Experimental
             Therapeutics},
   Volume = {343},
   Number = {2},
   Pages = {441-450},
   Year = {2012},
   Month = {November},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/22899752},
   Abstract = {Chronic nicotine administration increases α4β2 neuronal
             nicotinic acetylcholine receptor (nAChR) density in brain.
             This up-regulation probably contributes to the development
             and/or maintenance of nicotine dependence. nAChR
             up-regulation is believed to be triggered at the ligand
             binding site, so it is not surprising that other nicotinic
             ligands also up-regulate nAChRs in the brain. These other
             ligands include varenicline, which is currently used for
             smoking cessation therapy. Sazetidine-A (saz-A) is a newer
             nicotinic ligand that binds with high affinity and
             selectivity at α4β2* nAChRs. In behavioral studies, saz-A
             decreases nicotine self-administration and increases
             performance on tasks of attention. We report here that,
             unlike nicotine and varenicline, chronic administration of
             saz-A at behaviorally active and even higher doses does not
             up-regulate nAChRs in rodent brains. We used a newly
             developed method involving radioligand binding to measure
             the concentrations and nAChR occupancy of saz-A, nicotine,
             and varenicline in brains from chronically treated rats. Our
             results indicate that saz-A reached concentrations in the
             brain that were ∼150 times its affinity for α4β2* nAChRs
             and occupied at least 75% of nAChRs. Thus, chronic
             administration of saz-A did not up-regulate nAChRs despite
             it reaching brain concentrations that are known to bind and
             desensitize virtually all α4β2* nAChRs in brain. These
             findings reinforce a model of nicotine addiction based on
             desensitization of up-regulated nAChRs and introduce a
             potential new strategy for smoking cessation therapy in
             which drugs such as saz-A can promote smoking cessation
             without maintaining nAChR up-regulation, thereby potentially
             increasing the rate of long-term abstinence from
             nicotine.},
   Doi = {10.1124/jpet.112.198085},
   Key = {fds274319}
}

@article{fds274320,
   Author = {Roy, NM and Arpie, B and Lugo, J and Linney, E and Levin, ED and Cerutti,
             D},
   Title = {Brief embryonic strychnine exposure in zebrafish causes
             long-term adult behavioral impairment with indications of
             embryonic synaptic changes.},
   Journal = {Neurotoxicol Teratol},
   Volume = {34},
   Number = {6},
   Pages = {587-591},
   Year = {2012},
   Month = {November},
   ISSN = {0892-0362},
   url = {http://dx.doi.org/10.1016/j.ntt.2012.08.001},
   Abstract = {Zebrafish provide a powerful model of the impacts of
             embryonic toxicant exposure on neural development that may
             result in long-term behavioral dysfunction. In this study,
             zebrafish embryos were treated with 1.5mM strychnine for
             short embryonic time windows to induce transient changes in
             inhibitory neural signaling, and were subsequently raised in
             untreated water until adulthood. PCR analysis showed
             indications that strychnine exposure altered expression of
             some genes related to glycinergic, GABAergic and
             glutamatergic neuronal synapses during embryonic
             development. In adulthood, treated fish showed significant
             changes in swimming speed and tank diving behavior compared
             to controls. Taken together, these data show that a short
             embryonic exposure to a neurotoxicant can alter development
             of neural synapses and lead to changes in adult
             behavior.},
   Doi = {10.1016/j.ntt.2012.08.001},
   Key = {fds274320}
}

@article{fds274326,
   Author = {Swartzwelder, NA and Risher, ML and Abdelwahab, SH and D'Abo, A and Rezvani, AH and Levin, ED and Wilson, WA and Swartzwelder, HS and Acheson, SK},
   Title = {Effects of ethanol, Δ(9)-tetrahydrocannabinol, or their
             combination on object recognition memory and object
             preference in adolescent and adult male rats.},
   Journal = {Neurosci Lett},
   Volume = {527},
   Number = {1},
   Pages = {11-15},
   Year = {2012},
   Month = {October},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/22959891},
   Abstract = {Recent advances have been made in our understanding of the
             deleterious effects of both ethanol and THC on adolescent
             behavior and brain development. However, very little is
             known about the combined effects of EtOH+THC during
             adolescence, a time in which these drugs are often used
             together. The purpose of this experiment was to: (1)
             determine whether EtOH and/or THC induced greater working
             memory impairment in adolescent than adult male rats using
             the novel object recognition (NOR) task and (2) determine
             whether the EtOH+THC combination would produce a more potent
             additive effect in adolescents than adults when compared to
             these drugs alone. NOR was performed with a 24h delay under
             each of the four drug conditions: vehicle; 1.5g/kg ethanol;
             1.0mg/kg THC; and 1.5g/kg EtOH+1.0mg/kg THC, at 72h
             intervals. The results show that there was an age effect on
             working memory in NOR after the EtOH+THC challenge.
             Specifically, adolescent animals showed a preference for the
             familiar object whereas adults showed no preference for the
             novel or familiar object, the latter being characteristic of
             a classic working memory deficit. These effects were not
             dependent on changes in exploration across session, global
             activity across drug condition, or total object exploration.
             These novel findings clearly indicate that further
             understanding of this age-drug interaction is crucial to
             elucidating the influence that adolescent EtOH+THC use may
             have on repeated drug use and abuse later in
             life.},
   Doi = {10.1016/j.neulet.2012.08.037},
   Key = {fds274326}
}

@article{fds274318,
   Author = {Rezvani, AH and Cauley, MC and Johnson, EC and Gatto, GJ and Levin,
             ED},
   Title = {Effects of AZD3480, a neuronal nicotinic acetylcholine
             receptor agonist, and donepezil on dizocilpine-induced
             attentional impairment in rats.},
   Journal = {Psychopharmacology (Berl)},
   Volume = {223},
   Number = {3},
   Pages = {251-258},
   Year = {2012},
   Month = {October},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/22526540},
   Abstract = {BACKGROUND AND RATIONALE: Nicotinic acetylcholine systems
             play major roles in cognitive function. Nicotine and a
             variety of nicotinic agonists improve attention, and
             nicotinic antagonist exposure impairs it. This study was
             conducted to investigate the effect of a novel nicotinic
             receptor agonist at α4β2 nicotinic receptors (AZD3480) on
             attention and reversal of pharmacologically induced
             attentional impairment produced by the NMDA glutamate
             antagonist dizocilpine (MK-801). METHODS: Adult female
             Sprague-Dawley rats were trained to perform an operant
             visual signal detection task to a stable baseline of
             accuracy. The rats were then injected subcutaneously
             following a repeated measures, counter-balanced design with
             saline, AZD3480 (0.01, 0.1, and 1 mg/kg), dizocilpine (0.05
             mg/kg), or their combinations 30 min before the test. The
             effect of donepezil on the same pharmacologically induced
             attentional impairment was also tested. A separate group of
             rats was injected with donepezil (0.01, 0.1, and 1 mg/kg),
             dizocilpine (0.05 mg/kg), or their combinations, and their
             attention were assessed. Saline was the vehicle control.
             RESULTS: Dizocilpine caused a significant (p < 0.0005)
             impairment in percent correct performance. This attentional
             impairment was significantly (p < 0.0005) reversed by
             0.01 and 0.1 mg/kg of AZD3480. AZD3480 by itself did not
             alter the already high baseline control performance.
             Donepezil (0.01-1.0 mg/kg) also significantly
             (p < 0.005) attenuated the dizocilpine-induced
             attentional impairment. CONCLUSIONS: AZD3480, similar to
             donepezil, showed significant efficacy for counteracting the
             attentional impairment caused by the NMDA glutamate
             antagonist dizocilpine. Low doses of AZD3480 may provide
             therapeutic benefit for reversing attentional impairment in
             patients suffering from cognitive impairment due to
             glutamatergic dysregulation and likely other attentional
             disorders.},
   Doi = {10.1007/s00213-012-2712-2},
   Key = {fds274318}
}

@article{fds274317,
   Author = {Rezvani, AH and Lawrence, AJ and Arolfo, MP and Levin, ED and Overstreet, DH},
   Title = {Novel medication targets for the treatment of alcoholism:
             preclinical studies.},
   Journal = {Recent Pat Cns Drug Discov},
   Volume = {7},
   Number = {2},
   Pages = {151-162},
   Year = {2012},
   Month = {August},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/22574676},
   Abstract = {Alcoholism is a complex heterogeneous disease and a number
             of neurotransmitter and neuromodulator systems have been
             implicated in its manifestation. Consequently, it is
             unlikely that existing medications such as disulfiram
             (Antabuse®), naltrexone (ReVia®), acamprosate (Campral®))
             can be efficacious in every individual. Thus, the
             development of novel therapeutic agents with greater
             selectivity and less unwanted effects for the treatment of
             this disease is one of the major objectives of alcohol
             research. This review summarizes the findings of five novel
             compounds with different neuronal targets for treating
             alcoholism. These compounds include sazetidine-A, which
             selectively desensitizes α4β2 nicotinic receptors;
             carisbamate, a novel anti-epileptic agent; JNJ5234801, a
             novel anxiolytic agent; GS-455534, a highly selective
             inhibitor of mitochondrial aldehyde dehydrogenase; and
             JNJ-39220675, a selective histamine H3 antagonist. Inbred
             alcohol-preferring rats (iP), Fawn-Hooded (FH) rats, and P
             rats were used to evaluate the compounds. Naltrexone was
             used as a positive control in some experiments. All five
             compounds reduced alcohol consumption and preference. The
             mechanisms thought to underlie these effects suggest that,
             in addition to dopaminergic and opioidergic systems, other
             neuronal systems such as sodium channels (carisbamate),
             mitochondrial aldehyde dehydrogenase (GS-455534), 5-HT2
             receptors (JNJ-5234801), histamine H3 receptors
             (JNJ-39220675), and α4β2 nicotinic receptors
             (sazetidine-A) can be involved in alcohol drinking. Further
             work is necessary to confirm the exact mechanisms of action
             of each drug and to determine any viable targets for
             putative treatment of alcohol-use disorders. The article
             presents some promising patents on novel medication targets
             for the treatment of alcoholism.},
   Doi = {10.2174/157488912800673182},
   Key = {fds274317}
}

@article{fds274310,
   Author = {Larrauri, JA and Levin, ED},
   Title = {Differential effects of the antidepressant mirtazapine on
             amphetamine- and dizocilpine-induced PPI
             deficits.},
   Journal = {Pharmacol Biochem Behav},
   Volume = {102},
   Number = {1},
   Pages = {82-87},
   Year = {2012},
   Month = {July},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/22469866},
   Abstract = {Prepulse inhibition (PPI) refers to the decrease in motor
             startle response to salient sensory stimuli (pulses) when
             they are closely preceded in time by another more modest
             sensory stimulus (prepulse). PPI deficits can be induced by
             stimulation of dopamine receptors (e.g., amphetamine or
             apomorphine) or blockade of NMDA glutamate receptors (e.g.,
             dizocilpine or PCP). Previously we found that antagonists of
             α(2)-noradrenergic and H(1)-histaminergic receptors
             significantly attenuate PPI impairments caused by
             amphetamine or dizocilpine. In the current study we assessed
             the effects of the antidepressant mirtazapine, which has
             combined antagonist effects at α(2)-noradrenergic,
             H(1)-histaminergic and 5-HT serotonergic receptors, on
             amphetamine- and dizocilpine-induced PPI deficits. In
             Experiment 1, rats were tested for PPI of the startle
             response to a tactile air-puff stimulus after auditory
             prepulses of three different intensities. Drug treatments
             consisted of combinations of amphetamine (0 and 1mg/kg) and
             mirtazapine (0, 0.5, 1, 2, and 5mg/kg), with all rats
             receiving all drug doses and combinations with different
             counterbalanced orders. In Experiment 2, a different group
             of rats was tested with drug treatments consisting of
             combinations of dizocilpine (0 and 0.05 mg/kg) and
             mirtazapine (0, 0.5, 1, 2, and 5 mg/kg). In Experiment 1
             amphetamine (1 mg/kg) significantly reduced PPI whereas
             mirtazapine caused the opposite effect, with the highest
             dose of mirtazapine (5 mg/kg) effectively reversing the
             amphetamine-induced PPI deficit. In Experiment 2 dizocilpine
             (0.05 mg/kg) significantly reduced PPI, but mirtazapine did
             not have a significant effect on the inhibition of the
             startle response. These results indicate that the potential
             beneficial effects of combined α-adrenergic, 5-HT, and H(1)
             receptor blockade in counteracting PPI deficits may be
             associated to cases of sensorimotor gating disorders
             mediated by dopamine, but not necessarily to NMDA
             glutamate-induced PPI impairments.},
   Doi = {10.1016/j.pbb.2012.03.010},
   Key = {fds274310}
}

@article{fds274316,
   Author = {Johnson, JE and Slade, S and Wells, C and Petro, A and Sexton, H and Rezvani, AH and Brown, ML and Paige, MA and McDowell, BE and Xiao, Y and Kellar, KJ and Levin, ED},
   Title = {Assessing the effects of chronic sazetidine-A delivery on
             nicotine self-administration in both male and female
             rats.},
   Journal = {Psychopharmacology (Berl)},
   Volume = {222},
   Number = {2},
   Pages = {269-276},
   Year = {2012},
   Month = {July},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/22297831},
   Abstract = {RATIONALE: Sazetidine-A is a selective α4β2 nicotinic
             receptor desensitizing agent and partial agonist. It has
             been shown in previous studies to significantly reduce
             nicotine self-administration in rats after acute or repeated
             injections. However, the effects of continuous chronic
             infusions of sazetidine-A on maintenance of nicotine
             self-administration and relapse after abstinence have yet to
             be examined. OBJECTIVES: This study evaluated the efficacy
             of continuous sazetidine-A infusions (sc) over a period of 4
             weeks to reduce nicotine self-administration in male and
             female Sprague-Dawley rats. METHODS: Sazetidine-A was
             administered via Alzet osmotic minipumps to young adult
             female and male rats at doses of 0, 2 or 6 mg/kg/day for 4
             weeks. The effects of sazetidine-A on IV nicotine
             self-administration were examined in repeated 3-h sessions
             over the first 2 weeks of infusion followed by 1 week of
             forced abstinence from nicotine and 1 week of resumed
             nicotine access. RESULTS: The 6 mg/kg/day sazetidine-A dose
             significantly reduced overall nicotine self-administration
             compared with vehicle control across the sessions for both
             male (p < 0.001) and female (p < 0.05) rats. The
             lower 2 mg/kg/day sazetidine-A infusion dose was effective
             in reducing nicotine self-administration for male
             (p < 0.001), but not female rats. No attenuation in
             sazetidine-A effectiveness was seen over the course of the
             4-week treatment. In the vehicle control group, male rats
             self-administered significantly (p < 0.001) more
             nicotine than females. CONCLUSIONS: The continuing
             effectiveness of sazetidine-A in reducing nicotine
             self-administration in both male and female rats supports
             its promise as a new treatment to help people successfully
             quit smoking.},
   Doi = {10.1007/s00213-012-2642-z},
   Key = {fds274316}
}

@article{fds274314,
   Author = {Rezvani, AH and Timofeeva, O and Sexton, HG and DeCuir, D and Xiao, Y and Gordon, CJ and Kellar, KJ and Levin, ED},
   Title = {Effects of sazetidine-A, a selective α4β2* nicotinic
             receptor desensitizing agent, on body temperature regulation
             in mice and rats.},
   Journal = {Eur J Pharmacol},
   Volume = {682},
   Number = {1-3},
   Pages = {110-117},
   Year = {2012},
   Month = {May},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/22387853},
   Abstract = {Nicotine-induced hypothermia is well established, but the
             nicotinic receptor actions underlying this effect are not
             clear. Nicotine causes activation and desensitization at a
             variety of nicotinic receptor subtypes. Sazetidine-A
             [6-(5(((S)-azetidine-2-yl)methoxy)pyridine-3-yl)hex-5-yn-1-ol]
             is a novel compound that potently and selectively
             desensitizes α4β2* nicotinic receptors. The main goal of
             this study was to investigate the effects of sazetidine-A,
             on core body temperature (Tc) in mice and rats. Sazetidine-A
             effects on Tc and the interactions of sazetidine-A with
             nicotine and selective nicotinic antagonists were
             investigated to determine the receptor actions underlying
             nicotine-induced hypothermia. Adult male mice were injected
             with different dose of nicotine (0.2, 0.4 and 0.8 mg/kg),
             sazetidine-A (0.3, 1, and 3mg/kg), a mixture of nicotine
             (0.4 or 0.8 mg/kg) and sazetidine-A (0.3 or 0.6 mg/kg) or
             saline and Tc was monitored telemetrically. In another set
             of experiments, the interaction between sazetidine-A and
             dihydro-β-erythroidine (DHβE), an α4β2* nicotinic
             receptors antagonist, and methyllycaconitine (MLA), an α7
             antagonist, was investigated. Tc of mice was monitored
             following DHβE (1, 3 and 6 mg/kg), a combination of DHβE
             (3mg/kg) and sazetidine-A (0.6 mg/kg), MLA (1.5, 3 or 6
             mg/kg) or combination of MLA (6 mg/kg) and sazetidine (0.6
             mg/kg) or saline. The acute effect of sazetidine-A (1, 3,
             and 6 mg/kg) on rats Tc was also studied. Acute sazetidine-A
             caused a pronounced and long-lasting hypothermia in mice; Tc
             decreased to about 28°C at 100 min and recovered within 230
             min. The hypothermic effect of sazetidine in rats was much
             less in magnitude (about 3°C) and shorter in duration
             compared with that in mice. Nicotine co-administration with
             low doses of sazetidine potentiated the magnitude and
             duration of hypothermia in mice. The α4β2* nicotinic
             receptors antagonist DHβE significantly prolonged
             sazetidine-A-induced hypothermia but did not increase its
             depth. The α7 antagonist MLA caused a modest degree of
             hypothermia with relatively short duration in mice. MLA
             failed to counteract the sazetidine-A-induced hypothermia.
             Overall, our results show that pharmacological modulation of
             α4β2* nicotinic receptors elicits changes in body
             temperature that may involve desensitization of these
             receptors.},
   Doi = {10.1016/j.ejphar.2012.02.031},
   Key = {fds274314}
}

@article{fds274315,
   Author = {Levin, ED},
   Title = {α7-Nicotinic receptors and cognition.},
   Journal = {Curr Drug Targets},
   Volume = {13},
   Number = {5},
   Pages = {602-606},
   Year = {2012},
   Month = {May},
   ISSN = {1389-4501},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/22300026},
   Abstract = {Nicotinic α7 receptors have been shown in a variety of
             studies with animal models to play important roles in
             diverse components of cognitive function, including
             learning, memory and attention. Mice with α7 receptor
             knockouts show impairments in memory. Selective α7 agonists
             significantly improve learning, memory and attention. α7
             receptors in limbic structures such as the hippocampus and
             amygdala have been demonstrated to play critical roles in
             memory. Blockade of α7 receptors in these areas cause
             memory impairments. In the brains of people with
             schizophrenia α7 receptors are impaired. This may be
             related to pronounced cognitive impairments seen with
             schizophrenia. There has been a major effort to develop α7
             nicotinic agonists for helping to reverse cognitive
             impairment. These receptors are a promising target for
             development of therapeutic treatments for a variety of
             diseases of cognitive impairment including Alzheimer's
             disease, attention deficit hyperactivity disorder (ADHD) and
             schizophrenia.},
   Doi = {10.2174/138945012800398937},
   Key = {fds274315}
}

@article{fds274312,
   Author = {Hall, FS and Markou, A and Levin, ED and Uhl, GR},
   Title = {Mouse models for studying genetic influences on factors
             determining smoking cessation success in
             humans.},
   Journal = {Ann N Y Acad Sci},
   Volume = {1248},
   Number = {1},
   Pages = {39-70},
   Year = {2012},
   Month = {February},
   ISSN = {0077-8923},
   url = {http://dx.doi.org/10.1111/j.1749-6632.2011.06415.x},
   Abstract = {Humans differ in their ability to quit using addictive
             substances, including nicotine, the major psychoactive
             ingredient in tobacco. For tobacco smoking, a substantial
             body of evidence, largely derived from twin studies,
             indicates that approximately half of these individual
             differences in ability to quit are heritable genetic
             influences that likely overlap with those for other
             addictive substances. Both twin and molecular genetic
             studies support overlapping influences on nicotine addiction
             vulnerability and smoking cessation success, although there
             is little formal analysis of the twin data that support this
             important point. None of the current datasets provides
             clarity concerning which heritable factors might provide
             robust dimensions around which individuals differ in ability
             to quit smoking. One approach to this problem is to test
             mice with genetic variations in genes that contain human
             variants that alter quit success. This review considers
             which features of quit success should be included in a
             comprehensive approach to elucidate the genetics of quit
             success, and how those features may be modeled in
             mice.},
   Doi = {10.1111/j.1749-6632.2011.06415.x},
   Key = {fds274312}
}

@article{fds274313,
   Author = {Newhouse, P and Kellar, K and Aisen, P and White, H and Wesnes, K and Coderre, E and Pfaff, A and Wilkins, H and Howard, D and Levin,
             ED},
   Title = {Nicotine treatment of mild cognitive impairment: a 6-month
             double-blind pilot clinical trial.},
   Journal = {Neurology},
   Volume = {78},
   Number = {2},
   Pages = {91-101},
   Year = {2012},
   Month = {January},
   ISSN = {0028-3878},
   url = {http://dx.doi.org/10.1212/WNL.0b013e31823efcbb},
   Abstract = {OBJECTIVE: To preliminarily assess the safety and efficacy
             of transdermal nicotine therapy on cognitive performance and
             clinical status in subjects with mild cognitive impairment
             (MCI). METHODS: Nonsmoking subjects with amnestic MCI were
             randomized to transdermal nicotine (15 mg per day or
             placebo) for 6 months. Primary outcome variables were
             attentional improvement assessed with Connors Continuous
             Performance Test (CPT), clinical improvement as measured by
             clinical global impression, and safety measures. Secondary
             measures included computerized cognitive testing and patient
             and observer ratings. RESULTS: Of 74 subjects enrolled, 39
             were randomized to nicotine and 35 to placebo. 67 subjects
             completed (34 nicotine, 33 placebo). The primary cognitive
             outcome measure (CPT) showed a significant nicotine-induced
             improvement. There was no statistically significant effect
             on clinician-rated global improvement. The secondary outcome
             measures showed significant nicotine-associated improvements
             in attention, memory, and psychomotor speed, and
             improvements were seen in patient/informant ratings of
             cognitive impairment. Safety and tolerability for
             transdermal nicotine were excellent. CONCLUSION: This study
             demonstrated that transdermal nicotine can be safely
             administered to nonsmoking subjects with MCI over 6 months
             with improvement in primary and secondary cognitive measures
             of attention, memory, and mental processing, but not in
             ratings of clinician-rated global impression. We conclude
             that this initial study provides evidence for
             nicotine-induced cognitive improvement in subjects with MCI;
             however, whether these effects are clinically important will
             require larger studies. CLASSIFICATION OF EVIDENCE: This
             study provides Class I evidence that 6 months of transdermal
             nicotine (15 mg/day) improves cognitive test performance,
             but not clinical global impression of change, in nonsmoking
             subjects with amnestic MCI.},
   Doi = {10.1212/WNL.0b013e31823efcbb},
   Key = {fds274313}
}

@article{fds274308,
   Author = {Larrauri, JA and Rosenthal, MZ and Levin, ED and McClernon, FJ and Schmajuk, NA},
   Title = {Effects of unexpected changes in visual scenes on the human
             acoustic startle response and prepulse inhibition.},
   Journal = {Behav Processes},
   Volume = {89},
   Number = {1},
   Pages = {1-7},
   Year = {2012},
   Month = {January},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/22001728},
   Abstract = {Prepulse inhibition (PPI) refers to the process wherein
             startle responses to salient stimuli (e.g., startling sound
             pulses) are attenuated by the presentation of another
             stimulus (e.g., a brief pre-pulse) immediately before the
             startling stimulus. Accordingly, deficits in PPI reflect
             atypical sensorimotor gating that is linked to
             neurobehavioral systems underlying responsivity to
             emotionally evocative cues. Little is known about the
             effects of changes in visual contextual information in PPI
             among humans. In this study, the effects of introducing
             unexpected changes in the visual scenes presented on a
             computer monitor on the human auditory startle response and
             PPI were assessed in young adults. Based on our animal data
             showing that unexpected transitions from a dark to a light
             environment reduce the startle response and PPI in rats
             after the illumination transition, it was hypothesized that
             novel changes in visual scenes would produce similar effects
             in humans. Results show that PPI decreased when elements
             were added to or removed from visual scenes, and that this
             effect declined after repeated presentations of the modified
             scene, supporting the interpretation that the PPI reduction
             was due to novel information being processed. These findings
             are the first to demonstrate that novel visual stimuli can
             impair sensorimotor gating of auditory stimuli in
             humans.},
   Doi = {10.1016/j.beproc.2011.09.011},
   Key = {fds274308}
}

@article{fds274309,
   Author = {Larrauri, JA and Levin, ED},
   Title = {The α₂-adrenergic antagonist idazoxan counteracts
             prepulse inhibition deficits caused by amphetamine or
             dizocilpine in rats.},
   Journal = {Psychopharmacology (Berl)},
   Volume = {219},
   Number = {1},
   Pages = {99-108},
   Year = {2012},
   Month = {January},
   ISSN = {0033-3158},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/21710169},
   Abstract = {RATIONALE: Prepulse inhibition (PPI) is the reduction in
             startle response magnitude when intense stimuli are closely
             preceded by other weak stimuli. Animal models used to
             investigate sensorimotor gating deficits include both the
             stimulation of dopamine receptors (e.g., amphetamine or
             apomorphine) and the blockade of NMDA-glutamate receptors
             (e.g., dizocilpine or phencyclidine). OBJECTIVES: We
             assessed the effects of idazoxan (an α(2)-adrenergic
             antagonist) on amphetamine- and dizocilpine-induced PPI
             disruptions in adult female Sprague-Dawley rats. METHODS: In
             experiment 1, rats were tested for PPI in a bimodal paradigm
             with an acoustic prepulse and a tactile startle stimulus.
             Interactions of amphetamine (1 mg/kg) and idazoxan (0.5, 1,
             and 2 mg/kg) were assessed, with all rats receiving all drug
             doses in a counterbalanced order. In experiment 2,
             dizocilpine (0.05 mg/kg) and idazoxan (0.5, 1, and 2 mg/kg)
             interactions were analyzed. RESULTS: Amphetamine (1 mg/kg)
             caused a significant reduction in PPI. Both the 1- and
             2-mg/kg doses of idazoxan significantly counteracted this
             effect. Dizocilpine (.05 mg/kg) effectively inhibited PPI,
             and the 2-mg/kg idazoxan dose significantly counteracted
             this impairment. CONCLUSIONS: These results suggest that the
             effectiveness of atypical antipsychotics such as clozapine
             in counteracting sensorimotor gating deficits reported in
             previous studies (e.g., Swerdlow and Geyer, Pharmacol
             Biochem Behav 44:741-744, 1993; Bakshi et al., J Pharmacol
             Exp Ther 271:787-794, 1994) may be related to their
             α(2)-antagonist effects, which may be a critical mechanism
             of the therapeutic effects of atypical antipsychotics in
             schizophrenia.},
   Doi = {10.1007/s00213-011-2377-2},
   Key = {fds274309}
}

@article{fds274307,
   Author = {Levin, ED and Slade, S and Wells, C and Cauley, M and Petro, A and Vendittelli, A and Johnson, M and Williams, P and Horton, K and Rezvani,
             AH},
   Title = {Threshold of adulthood for the onset of nicotine
             self-administration in male and female rats.},
   Journal = {Behav Brain Res},
   Volume = {225},
   Number = {2},
   Pages = {473-481},
   Year = {2011},
   Month = {December},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/21854810},
   Abstract = {The great majority of tobacco addiction begins during
             adolescence. More heavily addicted smokers begin smoking
             earlier, but differentiating the neurobehavioral impact of
             nicotine self-administration during adolescence from
             self-selection bias (whereby people more prone to heavy
             addiction also begin earlier) cannot be ethically
             unconfounded in humans. The goals of this research were to
             determine the age threshold for the adult-like nicotine
             self-administration and determine sex differences. Male and
             female Sprague-Dawley rats were tested for nicotine
             self-administration starting at 4, 5, 6, 7, and 8 weeks of
             age in an operant FR1 schedule for IV nicotine (0.03
             mg/kg/infusion) in 45-min sessions for 2 weeks, with 1 week
             of enforced abstinence and 1 week of resumed access. This
             study replicated our earlier work that nicotine
             self-administration was increased in adolescent vs. adult
             rats and that the effect was more pronounced in adolescent
             males, but the increased nicotine self-administration was
             more persistent in adolescent-onset females. The age
             threshold for adult-like behavior was 6-7 weeks of age.
             Adolescent-onset nicotine self-administration had persisting
             effects of eggaurated increases of nicotine
             self-administration when fixed-ratio requirements for
             self-administration were lowered. Female rats that had begun
             nicotine self-administration during adolescence showed
             exaggerated increases in nicotine self-administration after
             a switch back to FR1 from FR8, indicating a lessened control
             over their self-administration. Adolescent-onset nicotine
             self-administration was not found to potentiate cocaine
             self-administration. Adolescent-onset nicotine
             self-administration causes persistent increases in nicotine
             self-administration in female rats even after they reach
             adulthood and disrupts control over self-administration
             behavior.},
   Doi = {10.1016/j.bbr.2011.08.005},
   Key = {fds274307}
}

@article{fds274306,
   Author = {Timofeeva, OA and Levin, ED},
   Title = {Glutamate and nicotinic receptor interactions in working
             memory: importance for the cognitive impairment of
             schizophrenia.},
   Journal = {Neuroscience},
   Volume = {195},
   Pages = {21-36},
   Year = {2011},
   Month = {November},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/21884762},
   Abstract = {This article reaches across disciplines to correlate results
             in molecular, cellular, behavioral, and clinical research to
             develop a more complete picture of how working memory (WM)
             functions. It identifies a new idea that deserves further
             investigation. NMDA glutamate receptors (NMDAR) are critical
             for memory function. NMDAR inhibition effectively reproduces
             principal manifestations of schizophrenia (SP), such as WM
             impairment and GABAergic deficit (mainly reduction of
             glutamic acid decarboxylase 67 (GAD67) and parvalbumin (PV)
             content). Nicotine and selective α7 nicotinic acetylcholine
             receptor (nAChR) agonists reduce WM impairments in patients
             with SP and reverse WM deficits in animals treated with
             NMDAR antagonists. The mechanism of this effect is unknown.
             Importantly, WM recovery occurs even before restoration of
             NMDAR blockade-induced molecular alterations, including
             reduced GAD67 in interneurons. Our insight into the
             cognitive-enhancing effect of α7 nAChR agonists,
             particularly in the animal models of SP, combines reviews of
             recent findings on glutamate and nicotinic receptor
             expression in the neuronal circuits involved in WM, the
             properties of these receptors, their implication in WM
             regulation, generation of rhythmic neuronal activity,
             resulting in a proposed hypothesis for further
             investigations. We suggest that (1) cortical/hippocampal
             interneurons, particularly PV positive, play a crucial role
             in WM and that impairment of these cells in SP could be
             behind the WM deficit; (2) activation of α7 nAChRs could
             restore calcium signaling and intrinsic properties of these
             interneurons, and associated with these events,
             computational capacity, gamma rhythmic activity, and WM
             would also be restored.},
   Doi = {10.1016/j.neuroscience.2011.08.038},
   Key = {fds274306}
}

@article{fds274302,
   Author = {Levin, ED and Sledge, D and Roach, S and Petro, A and Donerly, S and Linney, E},
   Title = {Persistent behavioral impairment caused by embryonic
             methylphenidate exposure in zebrafish.},
   Journal = {Neurotoxicol Teratol},
   Volume = {33},
   Number = {6},
   Pages = {668-673},
   Year = {2011},
   Month = {November},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/21741476},
   Abstract = {As more adults take the stimulant medication methylphenidate
             to treat attention deficit hyperactivity disorder (ADHD)
             residual type, the risk arises with regard to exposure
             during early development if people taking the medication
             become pregnant. We studied the neurobehavioral effects of
             methylphenidate in zebrafish. Zebrafish offer cellular
             reporter systems, continuous visual access and molecular
             interventions such as morpholinos to help determine critical
             mechanisms underlying neurobehavioral teratogenicity.
             Previously, we had seen that persisting neurobehavioral
             impairment in zebrafish with developmental chlorpyrifos
             exposure was associated with disturbed dopamine systems.
             Because methylphenidate is an indirect dopamine agonist, it
             was thought that it might also cause persistent behavioral
             impairment after developmental exposure. Zebrafish embryos
             were exposed to the ADHD stimulant medication
             methylphenidate 0-5 days post fertilization (12.5-50mg/l).
             They were tested for long-term behavioral effects as adults.
             Methylphenidate exposure (50mg/l) caused significant
             increases in dopamine, norepinepherine and serotonin on day
             6 but not day 30 after fertilization. In the novel tank
             diving test of predatory avoidance developmental
             methylphenidate (50mg/l) caused a significant reduction in
             the normal diving response. In the three-chamber spatial
             learning task early developmental methylphenidate (50mg/l)
             caused a significant impairment in choice accuracy. These
             data show that early developmental exposure of zebrafish to
             methylphenidate causes a long-term impairment in
             neurobehavioral plasticity. The identification of these
             functional deficits in zebrafish enables further studies
             with this model to determine how molecular and cellular
             mechanisms are disturbed to arrive at this compromised
             state.},
   Doi = {10.1016/j.ntt.2011.06.004},
   Key = {fds274302}
}

@article{fds274303,
   Author = {Sledge, D and Yen, J and Morton, T and Dishaw, L and Petro, A and Donerly,
             S and Linney, E and Levin, ED},
   Title = {Critical duration of exposure for developmental
             chlorpyrifos-induced neurobehavioral toxicity.},
   Journal = {Neurotoxicol Teratol},
   Volume = {33},
   Number = {6},
   Pages = {742-751},
   Year = {2011},
   Month = {November},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/21745564},
   Abstract = {Developmental exposure of rats to the pesticide chlorpyrifos
             (CPF) causes persistent neurobehavioral impairment. In a
             parallel series of studies with zebrafish, we have also
             found persisting behavioral dysfunction after developmental
             CPF exposure. We have developed a battery of measures of
             zebrafish behavior, which are reliable and sensitive to
             toxicant-induced damage. This study determined the critical
             duration of developmental CPF exposure for causing
             persisting neurobehavioral effects. Tests of sensorimotor
             response (tap startle response and habituation), stress
             response (novel tank diving test) and learning (3-chamber
             tank spatial discrimination) were conducted with adult
             zebrafish after early developmental CPF exposure. The CPF
             exposure level was 100 ng/ml with durations of 0-1, 0-2,
             0-3, 0-4 and 0-5 days after fertilization. Developmental CPF
             exposure had persisting behavioral effects in zebrafish
             tested as adults. In the tactile startle test, CPF exposed
             fish showed decreased habituation to startle and a trend
             toward increased overall startle response. In the novel tank
             exploration test, exposed fish showed decreased escape
             diving response and increased swimming activity. In the
             3-chamber learning test, the 0-5 day CPF exposure group had
             a significantly lower learning rate. There was evidence for
             persisting declines in brain dopamine and norepinepherine
             levels after developmental CPF exposure. In all of the
             measures the clearest persistent effects were seen in fish
             exposed for the full duration of five days after
             fertilization. In a follow-up experiment there were some
             indications for persisting behavioral effects after exposure
             during only the later phase of this developmental window.
             This study demonstrated the selective long-term
             neurobehavioral alterations caused by exposure to CPF in
             zebrafish. The zebrafish model can facilitate the
             determination of the molecular mechanisms underlying
             long-term neurobehavioral impairment after developmental
             toxicant exposure.},
   Doi = {10.1016/j.ntt.2011.06.005},
   Key = {fds274303}
}

@article{fds274304,
   Author = {Levin, ED and Tanguay, RL},
   Title = {Introduction to zebrafish: current discoveries and emerging
             technologies for neurobehavioral toxicology and
             teratology.},
   Journal = {Neurotoxicol Teratol},
   Volume = {33},
   Number = {6},
   Pages = {607},
   Year = {2011},
   Month = {November},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/22117689},
   Doi = {10.1016/j.ntt.2011.10.005},
   Key = {fds274304}
}

@article{fds274305,
   Author = {Yen, J and Donerly, S and Levin, ED and Linney, EA},
   Title = {Differential acetylcholinesterase inhibition of
             chlorpyrifos, diazinon and parathion in larval
             zebrafish.},
   Journal = {Neurotoxicol Teratol},
   Volume = {33},
   Number = {6},
   Pages = {735-741},
   Year = {2011},
   Month = {November},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/22036888},
   Abstract = {Zebrafish are increasingly used for developmental
             neurotoxicity testing because early embryonic events are
             easy to visualize, exposures are done without affecting the
             mother and the rapid development of zebrafish allows for
             high throughput testing. We used zebrafish to examine how
             exposures to three different organophosphorus pesticides
             (chlorpyrifos, diazinon and parathion) over the first five
             days of embryonic and larval development of zebrafish
             affected their survival, acetylcholinesterase (AChE)
             activity and behavior. We show that at non-lethal, equimolar
             concentrations, chlorpyrifos (CPF) is more effective at
             equimolar concentrations than diazinon (DZN) and parathion
             (PA) in producing AChE inhibition. As concentrations of DZN
             and PA are raised, lethality occurs before they can produce
             the degree of AChE inhibition observed with CPF at 300 nM.
             Because of its availability outside the mother at the time
             of fertilization, zebrafish provides a complementary model
             for studying the neurotoxicity of very early developmental
             exposures.},
   Doi = {10.1016/j.ntt.2011.10.004},
   Key = {fds274305}
}

@article{fds316113,
   Author = {Rezvani, AH and Cauley, M and Johnson, E and Levin,
             ED},
   Title = {Attentional improvement in rats with the nicotinic agonist
             AZ12564698 (AZD3480)},
   Journal = {Biochemical Pharmacology},
   Volume = {82},
   Number = {8},
   Pages = {1040-1041},
   Publisher = {Elsevier BV},
   Year = {2011},
   Month = {October},
   ISSN = {0006-2952},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000294513200069&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Doi = {10.1016/j.bcp.2011.07.046},
   Key = {fds316113}
}

@article{fds316082,
   Author = {Levin, ED},
   Title = {Using zebrafish to fill the gap between in vitro and rodent
             models for nicotinic drug development},
   Journal = {Biochemical Pharmacology},
   Volume = {82},
   Number = {8},
   Pages = {1038-1039},
   Publisher = {Elsevier BV},
   Year = {2011},
   Month = {October},
   ISSN = {0006-2952},
   url = {http://dx.doi.org/10.1016/j.bcp.2011.07.040},
   Doi = {10.1016/j.bcp.2011.07.040},
   Key = {fds316082}
}

@article{fds274300,
   Author = {Cippitelli, A and Rezvani, AH and Robinson, JE and Eisenberg, L and Levin, ED and Bonaventure, P and Motley, ST and Lovenberg, TW and Heilig, M and Thorsell, A},
   Title = {The novel, selective, brain-penetrant neuropeptide Y Y2
             receptor antagonist, JNJ-31020028, tested in animal models
             of alcohol consumption, relapse, and anxiety.},
   Journal = {Alcohol},
   Volume = {45},
   Number = {6},
   Pages = {567-576},
   Year = {2011},
   Month = {September},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/21145691},
   Abstract = {Neuropeptide Y (NPY) signaling has been shown to modulate
             stress responses and to be involved in regulation of alcohol
             intake and dependence. The present study explores the
             possibility that blockade of NPY Y2 autoreceptors using a
             novel, blood-brain barrier penetrant NPY Y2 receptor
             antagonist, JNJ-31020028 (N-(4-{4-[2-(diethylamino)-2-oxo-1-phenylethyl]piperazin-1-yl}-3-fluorophenyl)-2-pyridin-3-ylbenzamide),
             may achieve a therapeutically useful activation of the NPY
             system in alcohol- and anxiety-related behavioral models. We
             examined JNJ-31020028 in operant alcohol
             self-administration, stress-induced reinstatement to alcohol
             seeking, and acute alcohol withdrawal (hangover)-induced
             anxiety. Furthermore, we tested its effects on voluntary
             alcohol consumption in a genetic animal model of alcohol
             preference, the alcohol-preferring (P) rat. Neither systemic
             (0, 15, 30, and 40 mg/kg, subcutaneously [s.c.]) nor
             intracerebroventricular (0.0, 0.3, and 1.0 nmol/rat)
             administration of JNJ-31020028 affected alcohol-reinforced
             lever pressing or relapse to alcohol seeking behavior
             following stress exposure. Also, when its effects were
             tested on unlimited access to alcohol in P rats, preference
             for alcohol solution was transiently suppressed but without
             affecting voluntary alcohol intake. JNJ-31020028 (15 mg/kg,
             s.c.) did reverse the anxiogenic effects of withdrawal from
             a single bolus dose of alcohol on the elevated plus-maze,
             confirming the anxiolytic-like properties of NPY Y2
             antagonism. Our data do not support Y2 antagonism as a
             mechanism for reducing alcohol consumption or relapse-like
             behavior, but the observed effects on withdrawal-induced
             anxiety suggest that NPY Y2 receptor antagonists may be a
             putative treatment for the negative affective states
             following alcohol withdrawal.},
   Doi = {10.1016/j.alcohol.2010.09.003},
   Key = {fds274300}
}

@article{fds274301,
   Author = {Levin, ED and Johnson, JE and Slade, S and Wells, C and Cauley, M and Petro, A and Rose, JE},
   Title = {Lorcaserin, a 5-HT2C agonist, decreases nicotine
             self-administration in female rats.},
   Journal = {Journal of Pharmacology and Experimental
             Therapeutics},
   Volume = {338},
   Number = {3},
   Pages = {890-896},
   Year = {2011},
   Month = {September},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/21636655},
   Abstract = {Lorcaserin, a selective 5-hydroxytryptamine(2C) (5-HT(2C))
             agonist, has been shown to facilitate weight loss in obese
             populations. It was assessed for its efficacy in reducing
             nicotine self-administration in young adult female
             Sprague-Dawley rats. The effect of short-term doses
             (subcutaneous) on nicotine self-administration (0.03 mg/kg
             per infusion) with a fixed ratio 1 schedule was assessed in
             3-h sessions. Short-term lorcaserin doses (0.3125-20 mg/kg)
             were administered in a counterbalanced order. Significant
             reduction of nicotine self-administration was achieved with
             all of the short-term doses in this range. Tests of
             lorcaserin on locomotor activity detected prominent sedative
             effects at doses greater than 1.25 mg/kg with more modest
             transient effects seen at 0.625 to 1.25 mg/kg. Long-term
             effects of lorcaserin on locomotor activity were tested with
             repeated injections with 0.625 mg/kg lorcaserin 10 times
             over 2 weeks. This low lorcaserin dose did not cause an
             overall change in locomotor activity relative to that of
             saline-injected controls. Long-term lorcaserin (0.625 mg/kg)
             significantly reduced nicotine self-administration over a
             2-week period of repeated injections. Long-term lorcaserin
             at this same dose had no significant effects on food
             self-administration over the same 2-week period of repeated
             injections. These studies support development of the
             5-HT(2C) agonist lorcaserin to aid tobacco smoking
             cessation.},
   Doi = {10.1124/jpet.111.183525},
   Key = {fds274301}
}

@article{fds274299,
   Author = {Levin, ED and Bushnell, PJ and Rezvani, AH},
   Title = {Attention-modulating effects of cognitive
             enhancers.},
   Journal = {Pharmacol Biochem Behav},
   Volume = {99},
   Number = {2},
   Pages = {146-154},
   Year = {2011},
   Month = {August},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/21334367},
   Abstract = {Attention can be readily measured in experimental animal
             models. Animal models of attention have been used to better
             understand the neural systems involved in attention, how
             attention is impaired, and how therapeutic treatments can
             ameliorate attentional deficits. This review focuses on the
             ways in which animal models are used to better understand
             the neuronal mechanism of attention and how to develop new
             therapeutic treatments for attentional impairment. Several
             behavioral test methods have been developed for experimental
             animal studies of attention, including a 5-choice serial
             reaction time task (5-CSRTT), a signal detection task (SDT),
             and a novel object recognition (NOR) test. These tasks can
             be used together with genetic, lesion, pharmacological and
             behavioral models of attentional impairment to test the
             efficacy of novel therapeutic treatments. The most prominent
             genetic model is the spontaneously hypertensive rat (SHR).
             Well-characterized lesion models include frontal cortical or
             hippocampal lesions. Pharmacological models include
             challenge with the NMDA glutamate antagonist dizocilpine
             (MK-801), the nicotinic cholinergic antagonist mecamylamine
             and the muscarinic cholinergic antagonist scopolamine.
             Behavioral models include distracting stimuli and attenuated
             target stimuli. Important validation of these behavioral
             tests and models of attentional impairments for developing
             effective treatments for attentional dysfunction is the fact
             that stimulant treatments effective for attention deficit
             hyperactivity disorder (ADHD), such as methylphenidate
             (Ritalin®), are effective in the experimental animal
             models. Newer lines of treatment including nicotinic
             agonists, α4β2 nicotinic receptor desensitizers, and
             histamine H₃ antagonists, have also been found to be
             effective in improving attention in these animal models.
             Good carryover has also been seen for the attentional
             improvement caused by nicotine in experimental animal models
             and in human populations. Animal models of attention can be
             effectively used for the development of new treatments of
             attentional impairment in ADHD and other syndromes in which
             have attentional impairments occur, such as Alzheimer's
             disease and schizophrenia.},
   Doi = {10.1016/j.pbb.2011.02.008},
   Key = {fds274299}
}

@article{fds274298,
   Author = {Rezvani, AH and Cauley, M and Sexton, H and Xiao, Y and Brown, ML and Paige, MA and McDowell, BE and Kellar, KJ and Levin,
             ED},
   Title = {Sazetidine-A, a selective α4β2 nicotinic acetylcholine
             receptor ligand: effects on dizocilpine and
             scopolamine-induced attentional impairments in female
             Sprague-Dawley rats.},
   Journal = {Psychopharmacology (Berl)},
   Volume = {215},
   Number = {4},
   Pages = {621-630},
   Year = {2011},
   Month = {June},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/21274704},
   Abstract = {BACKGROUND: Neuronal nicotinic receptor systems have been
             shown to play key roles in cognition. Nicotine and nicotinic
             analogs improve attention and nicotinic antagonists impair
             it. This study was conducted to investigate the role of
             α4β2 nicotinic receptors in sustained attention using a
             novel selective α4β2 nicotinic receptor ligand,
             sazetidine-A. METHODS: Female rats were trained to perform
             the signal detection task to a stable baseline of accuracy.
             The rats were injected with saline, sazetidine-A (0.01,
             0.03, and 0.1 mg/kg), dizocilpine (0.05 mg/kg), or their
             combination; or, in another experiment, the rats were
             injected with the same doses of sazetidine-A, scopolamine
             (0.02 mg/kg), or their combination. RESULTS: Percent hit
             and percent correct rejection showed that dizocilpine caused
             significant (p < 0.025) impairments in performance,
             which were significantly reversed by each of the
             sazetidine-A doses. Response omissions were significantly
             (p < 0.05) increased by dizocilpine, and this was also
             significantly reversed by each of the sazetidine-A doses.
             None of the sazetidine-A doses had significant effects on
             hit, correct rejection, or response omissions when given
             alone. Scopolamine also caused significant (p < 0.0005)
             impairments in percent hit and percent correct rejection and
             increased response omissions, which were significantly
             attenuated by all the sazetidine-A doses for percent hit and
             response omissions and by the highest dose of sazetidine-A
             for percent correct rejection. Both scopolamine and
             dizocilpine significantly (p < 0.0005) increased
             response latency, an effect which was significantly
             attenuated by sazetidine-A coadministration. CONCLUSIONS:
             These studies imply an important role for α4β2 nicotinic
             receptors in improving sustained attention under conditions
             that disrupt it. Very low doses of sazetidine-A or drugs
             with a similar profile may provide therapeutic benefit for
             reversing attentional impairment in patients suffering from
             mental disorders and/or cognitive impairment.},
   Doi = {10.1007/s00213-010-2161-8},
   Key = {fds274298}
}

@article{fds274323,
   Author = {Schramm-Sapyta, NL and Cauley, MC and Stangl, DK and Glowacz, S and Stepp, KA and Levin, ED and Kuhn, CM},
   Title = {Role of individual and developmental differences in
             voluntary cocaine intake in rats.},
   Journal = {Psychopharmacology (Berl)},
   Volume = {215},
   Number = {3},
   Pages = {493-504},
   Year = {2011},
   Month = {June},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/21347641},
   Abstract = {RATIONALE: Early-onset drug taking is associated with
             increased likelihood of addiction, but it is unclear whether
             early onset is causal in development of addiction. Many
             other factors are associated with increased risk of
             addiction and also promote early intake. Here, a rodent
             model is used to explore the causality of early onset in
             development of self-administration and addiction-like
             behavior and to examine factors that promote
             self-administration. METHODS: We used cocaine
             self-administration to examine drug taking and
             addiction-like behavior in adolescent and adult rats a
             priori characterized for their locomotor responses to
             novelty and cocaine and behavior in the light-dark task.
             RESULTS: Adolescent animals initially sought more cocaine
             than adults. However, as the adolescents matured, their
             intake fell and they did not differ from adults in terms of
             unreinforced lever-pressing, extinction or reinstatement
             behavior. For both age groups, self-administration was
             positively correlated with the locomotor response to
             novelty, the locomotor response to cocaine, and with time in
             light in the light-dark task. The rats that were insensitive
             to cocaine's locomotor effects and that spent the least time
             in light in the light-dark task sought the least cocaine,
             appearing to be "protected" from the reinforcing effects of
             cocaine. There was no difference between the two age groups
             in appearance of this "protected" phenotype. CONCLUSIONS:
             These results suggest that early onset of drug taking may
             promote increased use, but does not promote progression to
             addiction-like behavior. Furthermore, protective factors,
             such as innate anxiety and insensitivity to cocaine's
             pharmacological effects, function across developmental
             stages.},
   Doi = {10.1007/s00213-011-2216-5},
   Key = {fds274323}
}

@article{fds274296,
   Author = {Levin, ED and Slade, S and Wells, C and Petro, A and Rose,
             JE},
   Title = {D-cycloserine selectively decreases nicotine
             self-administration in rats with low baseline levels of
             response.},
   Journal = {Pharmacol Biochem Behav},
   Volume = {98},
   Number = {2},
   Pages = {210-214},
   Year = {2011},
   Month = {April},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/21192967},
   Abstract = {Expanding the variety of treatments available to aid smoking
             cessation will allow the treatments to be customized to
             particular types of smokers. The key is to understand which
             subpopulations of smokers respond best to which treatment.
             This study used adult female Sprague-Dawley rats to evaluate
             the efficacy of D-cycloserine, a partial NMDA glutamate
             receptor agonist, in reducing nicotine self-administration.
             Rats were trained to self-administer nicotine (0.03
             mg/kg/infusion, i.v.) via operant lever response (FR1) with
             a secondary visual reinforcer. Two studies of D-cycloserine
             effects on nicotine self-administration were conducted: an
             acute dose-effect study (0, 10, 20 and 40 mg/kg, s.c.) and a
             chronic study with 40 mg/kg given before each test session
             for two weeks. Effects on rats with low or high pretreatment
             baseline levels of nicotine self-administration were
             assessed. In the acute study there was a significant
             interaction of D-cycloserine×baseline level of nicotine
             self-administration. In the low baseline group, 10 mg/kg
             D-cycloserine significantly decreased nicotine
             self-administration. In the high baseline group, 40 mg/kg
             significantly increased nicotine self-administration. In the
             repeated injection study, there was also a significant
             interaction of d-cycloserine×baseline level of nicotine
             self-administration. Chronic D-cycloserine significantly
             reduced nicotine self-administration selectively in rats
             with low baseline nicotine use, but was ineffective with the
             rats with higher levels of baseline nicotine
             self-administration. NMDA glutamate treatments may be
             particularly useful in helping lighter smokers successfully
             quit smoking, highlighting the need for diverse treatments
             for different types of smokers.},
   Doi = {10.1016/j.pbb.2010.12.023},
   Key = {fds274296}
}

@article{fds274297,
   Author = {Galici, R and Rezvani, AH and Aluisio, L and Lord, B and Levin, ED and Fraser, I and Boggs, J and Welty, N and Shoblock, JR and Motley, ST and Letavic, MA and Carruthers, NI and Dugovic, C and Lovenberg, TW and Bonaventure, P},
   Title = {JNJ-39220675, a novel selective histamine H3 receptor
             antagonist, reduces the abuse-related effects of alcohol in
             rats.},
   Journal = {Psychopharmacology (Berl)},
   Volume = {214},
   Number = {4},
   Pages = {829-841},
   Year = {2011},
   Month = {April},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/21086115},
   Abstract = {RATIONALE: A few recent studies suggest that brain histamine
             levels and signaling via H(3) receptors play an important
             role in modulation of alcohol stimulation and reward in
             rodents. OBJECTIVE: The present study characterized the
             effects of a novel, selective, and brain penetrant H(3)
             receptor antagonist (JNJ-39220675) on the reinforcing
             effects of alcohol in rats. METHODS: The effect of
             JNJ-39220675 on alcohol intake and alcohol relapse-like
             behavior was evaluated in selectively bred
             alcohol-preferring (P) rats using the standard two-bottle
             choice method. The compound was also tested on operant
             alcohol self administration in non-dependent rats and on
             alcohol-induced ataxia using the rotarod apparatus. In
             addition, alcohol-induced dopamine release in the nucleus
             accumbens was tested in freely moving rats. RESULTS:
             Subcutaneous administration of the selective H(3) receptor
             antagonist dose-dependently reduced both alcohol intake and
             preference in alcohol-preferring rats. JNJ-39220675 also
             reduced alcohol preference in the same strain of rats
             following a 3-day alcohol deprivation. The compound
             significantly and dose-dependently reduced alcohol
             self-administration without changing saccharin
             self-administration in alcohol non-dependent rats.
             Furthermore, the compound did not change the ataxic effects
             of alcohol, alcohol elimination rate, nor alcohol-induced
             dopamine release in nucleus accumbens. CONCLUSIONS: These
             results indicate that blockade of H(3) receptor should be
             considered as a new attractive mechanism for the treatment
             of alcoholism.},
   Doi = {10.1007/s00213-010-2092-4},
   Key = {fds274297}
}

@article{fds274294,
   Author = {Powers, CM and Levin, ED and Seidler, FJ and Slotkin,
             TA},
   Title = {Silver exposure in developing zebrafish produces persistent
             synaptic and behavioral changes.},
   Journal = {Neurotoxicol Teratol},
   Volume = {33},
   Number = {2},
   Pages = {329-332},
   Year = {2011},
   Month = {March},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/21035540},
   Abstract = {Environmental silver exposures are increasing due to the use
             of silver nanoparticles, which exert antimicrobial actions
             by releasing Ag+, a suspected developmental neurotoxicant.
             We evaluated the long-term neurochemical and behavioral
             effects of embryonic Ag+ exposure in zebrafish at
             concentrations that had no overt effects on morphological
             development. Exposure to 0.03, 0.1 or 0.3 μM Ag+ during the
             first five days post-fertilization caused elevations in both
             dopamine and serotonin turnover in the adult zebrafish brain
             without affecting basal neurotransmitter levels. Consistent
             with these synaptic effects, Ag+-exposed fish showed a
             faster acquisition of avoidance behavior in a three-chamber
             test apparatus, without any change in response latency or
             overall swimming ability. Our results indicate that Ag+ is a
             developmental neurotoxicant that causes persistent
             neurobehavioral effects, reinforcing health concerns about
             Ag+ released from silver nanoparticles.},
   Doi = {10.1016/j.ntt.2010.10.006},
   Key = {fds274294}
}

@article{fds274293,
   Author = {Levin, ED and Slade, S and Wells, C and Pruitt, M and Cousins, V and Cauley, M and Petro, A and Hampton, D and Rose, J},
   Title = {Histamine H(1) antagonist treatment with pyrilamine reduces
             nicotine self-administration in rats.},
   Journal = {Eur J Pharmacol},
   Volume = {650},
   Number = {1},
   Pages = {256-260},
   Year = {2011},
   Month = {January},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/20951696},
   Abstract = {Nicotine has been definitively shown to be critically
             involved in the neural bases of tobacco addiction. However,
             nicotine releases a wide variety of neurotransmitters.
             Nicotine-induced dopamine release has been shown to play a
             key role in facilitating nicotine self-administration. Other
             transmitter systems may also play important roles in the
             pharmacological effects of nicotine and may provide
             important leads for combating nicotine self-administration.
             Clozapine, an antipsychotic drug, which blocks a variety of
             different transmitter receptors including serotonin 5HT(2)
             and histamine H(1) receptors, has been found to decrease
             smoking. Previously we found that the serotonin 5HT(2)
             antagonist, ketanserin, significantly reduced nicotine
             self-administration. In the current study, we assessed
             histamine H(1) receptor interaction with nicotine
             self-administration. Young adult female Sprague-Dawley rats
             were fitted with IV catheters and trained to self-administer
             nicotine (0.03mg/kg/infusion). Acute doses of 40mg/kg of
             pyrilamine, a histamine H(1) antagonist, significantly
             reduced nicotine self-administration. We also found that
             repeated injections (20mg/kg) or chronic infusion via
             osmotic minipumps (50mg/kg/day) of pyrilamine also
             significantly decreased nicotine self-administration. The
             peripherally restricted H(1) antagonist ebastine was
             ineffective in reducing nicotine self-administration,
             pointing to central H(1) receptor blockade as key for the
             effectiveness of pyrilamine. H(1) antagonists may be a
             promising avenue to explore for new treatments to aid
             smoking cessation.},
   Doi = {10.1016/j.ejphar.2010.10.013},
   Key = {fds274293}
}

@article{fds274292,
   Author = {Levin, ED},
   Title = {Nicotinic receptor systems and neurobehavioral function in
             zebrafish},
   Journal = {Neuromethods},
   Volume = {52},
   Pages = {89-100},
   Publisher = {Humana Press},
   Year = {2011},
   Month = {January},
   ISSN = {0893-2336},
   url = {http://dx.doi.org/10.1007/978-1-60761-922-2_4},
   Abstract = {Nicotinic acetylcholine receptors appear to be quite ancient
             phylogenetically and are used in the nervous systems of a
             great number of species across broad parts of the animal
             kingdom. They play important roles in a variety of
             neurobehavioral functions from neuromuscular activation to
             cognitive function. Nicotinic receptor function is an
             excellent field in which to assess the potential
             commonalities of neurobehavioral functions across animal
             species. Nicotinic receptors are remarkably consistent
             across species and the behavioral effects of nicotinic
             treatments have been very well determined in mammals. Since
             zebrafish are an emerging aquatic model for studying
             neurobehavioral function, we have determined the effects of
             nicotine, the prototypic nicotinic agonist as well as
             nicotinic antagonists on cognitive function, exploratory
             behavior and stress response in a series of behavioral tests
             we have developed to reliably index these behavioral
             functions. The overall hypothesis of this line of
             investigation was that nicotine would have similar
             behavioral effects in zebrafish as in mammals when analogous
             tests of behavioral function are used. As with mammalian
             species, nicotine significantly improves learning and memory
             at low to moderate doses in zebrafish with an inverted
             J-shaped dose-effect function. The nicotine-induced learning
             improvement in zebrafish is reversed with the nicotinic
             antagonist mecamylamine and is accompanied by increased
             brain dopamine metabolite levels, an effect which is also
             reversed with mecamylamine. Also, as in mammals, nicotine
             has anxiolytic effects in zebrafish. Nicotine significantly
             reduces bottom dwelling in the novel tank diving task. This
             effect is reversed by either α7 or α4β2 nicotinic
             antagonist coadministration. In many respects nicotine has
             similar effects in zebrafish as in rodents and humans. These
             studies point to the value of zebrafish as models of human
             neurobehavioral function. © 2011 Springer Science+Business
             Media, LLC.},
   Doi = {10.1007/978-1-60761-922-2_4},
   Key = {fds274292}
}

@article{fds274295,
   Author = {Levin, ED},
   Title = {Zebrafish assessment of cognitive improvement and
             anxiolysis: filling the gap between in vitro and rodent
             models for drug development.},
   Journal = {Reviews in the Neurosciences},
   Volume = {22},
   Number = {1},
   Pages = {75-84},
   Year = {2011},
   ISSN = {0334-1763},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/21615262},
   Abstract = {Zebrafish can provide a valuable animal model to screen
             potential cognitive enhancing and anxiolytic drugs. They are
             economical and can provide a relatively quick indication of
             possible functional efficacy. In as much as they have a
             complex nervous system and elaborate behavioral repertoire,
             zebrafish can provide a good intermediate model between in
             vitro receptor and cell-based assays and classic mammalian
             models for drug screening. In addition, the variety of
             molecular tools available in zebrafish makes them
             outstanding models for helping to determine the
             neuromolecular mechanisms for psychoactive drugs. However,
             to use zebrafish as a translational model we must have
             validated, sensitive and efficient behavioral tests. In a
             series of studies, our lab has developed tests of cognitive
             function and stress response, which are sensitive to drug
             effects in a similar manner as rodent models and humans for
             cognitive enhancement and alleviating stress response. In
             particular, the three-chamber task for learning and memory
             was shown to be sensitive to the cognitive enhancing effects
             of nicotine and has been useful in helping to determine
             neural mechanisms crucial for nicotinic-induced cognitive
             enhancement. The novel tank diving test was shown to be a
             valid and efficient test of stress response. It is sensitive
             to the reduction in stress-related behaviors due to the
             amxiolytic drugs diazepam and buspirone but not
             chlordiazepoxide. Nicotine also causes stress alleviating
             effects which can be interpreted as anxiolytic effects.
             Zebrafish models of behavioral pharmacology can be useful to
             efficiently screen test compounds for drug development and
             can be useful in helping to determine the mechanisms crucial
             for new therapeutic treatments of neurobehavioral
             impairments.},
   Doi = {10.1515/RNS.2011.009},
   Key = {fds274295}
}

@article{fds274289,
   Author = {Levin, ED and Hampton, D and Rose, JE},
   Title = {IV nicotine self-administration in rats using the
             consummatory operant licking response.},
   Journal = {Physiol Behav},
   Volume = {101},
   Number = {5},
   Pages = {755-758},
   Year = {2010},
   Month = {December},
   ISSN = {0031-9384},
   url = {http://dx.doi.org/10.1016/j.physbeh.2010.08.016},
   Abstract = {Nicotine self-administered by tobacco smoking or chewing is
             very addictive in humans. Rat models have been developed in
             which nicotine is self-administered IV by the rats pressing
             a lever. However the reinforcing value of nicotine is much
             less in these models than the addictiveness of human tobacco
             use would indicate. The IV nicotine self-administration
             operant lever press model does not fully capture important
             aspects of tobacco use in humans. Conditioned oral
             consumption actions of smoking or chewing tobacco may play
             important roles in tobacco addiction. Neural circuitry
             underlying essential food consummatory responses may
             facilitate consummatory aspects of tobacco intake. To
             capture this motor consummatory aspect of tobacco addiction
             in the rat model of nicotine self-administration, we have
             developed a method of using a licking response instead of a
             lever press to self-administer IV nicotine. Sprague-Dawley
             rats were trained to lick one of two waterspouts for IV
             nicotine (0.03mg/kg/infusion). With the licking response
             rats self-administered stable nicotine levels throughout 24
             sessions (45min each) of testing. The number of total
             licks/session significantly increased in a linear fashion
             over that period. The number of licks/infusion was
             substantial, rising steadily with training to an average of
             over 100 licks/infusion. Including the consummatory motor
             act with nicotine self-administration could help better
             model the compulsive aspects of tobacco addiction in
             humans.},
   Doi = {10.1016/j.physbeh.2010.08.016},
   Key = {fds274289}
}

@article{fds274191,
   Author = {Timofeeva, OA and Levin, ED},
   Title = {Lasting Behavioral Consequences of Organophosphate Pesticide
             Exposure During Development},
   Pages = {837-846},
   Publisher = {Elsevier},
   Year = {2010},
   Month = {December},
   url = {http://dx.doi.org/10.1016/B978-0-12-374367-1.00033-1},
   Abstract = {This chapter defines the vulnerability of the developing
             nervous system to organophosphate pesticides, in terms of
             cognitive functions, social and sex-related behavioral
             patterns, and body weight regulation. Impaired
             neurobehavioral development of children has been
             significantly linked in epidemiological studies with
             exposure to pesticides. Environmental epidemiological
             studies are essential for identifying toxic risks, but like
             any single scientific approach they have limitations.
             Determining the cause-and-effect relationship beyond
             significant association is a challenge. Significant
             behavioral alterations are reported after short-term,
             low-dose exposure to a variety of organophosphates during
             development. Because these effects were observed at doses
             that do not significantly inhibit acetylcholinesterase,
             other mechanisms in addition to inhibition of this important
             enzyme should be considered. The aim of toxicology is to be
             a predictive science, to prevent toxic damage. Animal model
             studies can work in concert with epidemiological research to
             resolve many of these issues. With regard to organophosphate
             (OP) pesticide-induced developmental neurobehavioral
             toxicity, laboratory animal model studies have clearly
             demonstrated that the developing nervous system is quite
             vulnerable to detrimental effects of OP pesticides, even if
             exposure was short-term and at doses that did not cause much
             inhibition of acetylcholinesterase. © 2010 Elsevier Inc.
             All rights reserved.},
   Doi = {10.1016/B978-0-12-374367-1.00033-1},
   Key = {fds274191}
}

@article{fds274290,
   Author = {Larrauri, JA and Levin, ED},
   Title = {PPI deficit induced by amphetamine is attenuated by the
             histamine H1 antagonist pyrilamine, but is exacerbated by
             the serotonin 5-HT2 antagonist ketanserin.},
   Journal = {Psychopharmacology (Berl)},
   Volume = {212},
   Number = {4},
   Pages = {551-558},
   Year = {2010},
   Month = {December},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/20811878},
   Abstract = {RATIONALE: Prepulse inhibition (PPI) of the startle response
             is a classic model of sensorimotor gating. Robust PPI
             impairments can be induced by dopamine agonists such as the
             indirect agonist amphetamine. The antipsychotic clozapine
             can attenuate PPI impairment induced by dopamine agonists.
             Clozapine is a complex drug with antagonistic effects on a
             variety of receptors, including serotonin and histamine. The
             relative contribution of its component actions to its
             efficacy is still unclear. OBJECTIVES: To better
             characterize the role of histamine and serotonin receptors
             in the modulation of PPI in rats, we studied the effects of
             the H(1) histamine antagonist pyrilamine (10, 20, and 40
             mg/kg) on amphetamine-induced (1 mg/kg) PPI deficits
             (Experiment 1); and the interaction of pyrilamine (20 mg/kg)
             with the 5-HT(2) antagonist ketanserin (1 and 2 mg/kg) on
             the amphetamine-induced PPI disruption (Experiment 2).
             METHODS: Tactile startle stimuli consisted of 30 PSI
             air-puffs. Three acoustic prepulse intensity levels were
             used: 68, 71, and 77 dB, presented on a 65-dB background
             noise. In both experiments, all animals received all drug
             doses and combinations with different counterbalanced
             orders. RESULTS: Pyrilamine (20 mg/kg) was effective in
             counteracting the PPI impairment caused by amphetamine
             administration, whereas ketanserin exacerbated the
             amphetamine-induced PPI deficit. CONCLUSIONS: Based on its
             ability to reverse amphetamine-induced PPI deficits,
             blockade of histamine H(1) receptors seems to contribute to
             the therapeutic effect of the antipsychotic clozapine.
             Serotonin 5-HT(2)-receptor blockade, though, does not appear
             to contribute to this effect, and may in fact detract from
             it.},
   Doi = {10.1007/s00213-010-2005-6},
   Key = {fds274290}
}

@article{fds274291,
   Author = {Aschner, M and Levin, ED and Suñol, C and Olopade, JO and Helmcke, KJ and Avila, DS and Sledge, D and Ali, RH and Upchurch, L and Donerly, S and Linney, E and Forsby, A and Ponnuru, P and Connor,
             JR},
   Title = {Gene-environment interactions: neurodegeneration in
             non-mammals and mammals.},
   Journal = {Neurotoxicology},
   Volume = {31},
   Number = {5},
   Pages = {582-588},
   Year = {2010},
   Month = {September},
   ISSN = {0161-813X},
   url = {http://dx.doi.org/10.1016/j.neuro.2010.03.008},
   Abstract = {The understanding of how environmental exposures interact
             with genetics in central nervous system dysfunction has
             gained great momentum in the last decade. Seminal findings
             have been uncovered in both mammalian and non-mammalian
             model in large result of the extraordinary conservation of
             both genetic elements and differentiation processes between
             mammals and non-mammalians. Emerging model organisms, such
             as the nematode and zebrafish have made it possible to
             assess the effects of small molecules rapidly,
             inexpensively, and on a miniaturized scale. By combining the
             scale and throughput of in vitro screens with the
             physiological complexity and traditional animal studies,
             these models are providing relevant information on molecular
             events in the etiology of neurodegenerative disorders. The
             utility of these models is largely driven by the functional
             conservation seen between them and higher organisms,
             including humans so that knowledge obtained using
             non-mammalian model systems can often provide a better
             understanding of equivalent processes, pathways, and
             mechanisms in man. Understanding the molecular events that
             trigger neurodegeneration has also greatly relied upon the
             use of tissue culture models. The purpose of this summary is
             to provide-state-of-the-art review of recent developments of
             non-mammalian experimental models and their utility in
             addressing issues pertinent to neurotoxicity (Caenorhabditis
             elegans and Danio rerio). The synopses by Aschner and Levin
             summarize how genetic mutants of these species can be used
             to complement the understanding of molecular and cellular
             mechanisms associated with neurobehavioral toxicity and
             neurodegeneration. Next, studies by Suñol and Olopade
             detail the predictive value of cultures in assessing
             neurotoxicity. Suñol and colleagues summarize present novel
             information strategies based on in vitro toxicity assays
             that are predictive of cellular effects that can be
             extrapolated to effects on individuals. Olopade and
             colleagues describe cellular changes caused by sodium
             metavanadate (SMV) and demonstrate how rat primary astrocyte
             cultures can be used as predicitive tools to assess the
             neuroprotective effects of antidotes on vanadium-induced
             astrogliosis and demyelination.},
   Doi = {10.1016/j.neuro.2010.03.008},
   Key = {fds274291}
}

@article{fds274287,
   Author = {Rezvani, AH and Slade, S and Wells, C and Petro, A and Lumeng, L and Li,
             T-K and Xiao, Y and Brown, ML and Paige, MA and McDowell, BE and Rose, JE and Kellar, KJ and Levin, ED},
   Title = {Effects of sazetidine-A, a selective alpha4beta2 nicotinic
             acetylcholine receptor desensitizing agent on alcohol and
             nicotine self-administration in selectively bred
             alcohol-preferring (P) rats.},
   Journal = {Psychopharmacology (Berl)},
   Volume = {211},
   Number = {2},
   Pages = {161-174},
   Year = {2010},
   Month = {August},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/20535453},
   Abstract = {RATIONALE: Manipulations of nicotinic cholinergic receptors
             have been shown to influence both alcohol and nicotine
             intake. Sazetidine-A [6-(5(((S)-azetidine-2-yl)methoxy)pyridine-3-yl)hex-5-yn-1-ol]
             is a novel compound that potently and selectively
             desensitizes alpha4beta2 nicotinic receptors with only
             modest receptor activation. OBJECTIVES: The goal of the
             present study was to examine the effects of sazetidine-A on
             alcohol and nicotine self-administration in
             alcohol-preferring (P) rats. METHODS: P rats were given the
             choice of water or alcohol. Once stable baselines were
             established, the acute (0, 0.1, 0.3, 1, and 3 mg/kg, s.c.)
             and chronic (3 mg/kg for 10 days) effects of sazetidine-A on
             alcohol intake were assessed. Naltrexone (2.5 mg/kg) served
             as a positive control. The effect of sazetidine-A (3 mg/kg)
             and naltrexone (4 mg/kg) on saccharin (0.2%) preference was
             also assessed. In addition, the acute effects of
             sazetidine-A (3 mg/kg) and naltrexone (4 mg/kg) on alcohol
             intake after alcohol deprivation were evaluated. In another
             experiment, the effects of sazetidine-A (0, 1, or 3 mg/kg)
             on i.v. nicotine self-administration in P and NP rats were
             assessed. RESULTS: Sazetidine-A caused a dose-dependent
             reduction in alcohol intake. Chronic sazetidine-A also
             effectively reduced alcohol intake until the seventh day of
             treatment, when partial tolerance appeared to develop. In
             the post-deprivation study, sazetidine-A significantly
             reduced alcohol intake and preference. Sazetidine-A at 3
             mg/kg significantly reduced nicotine self-administration in
             both lines. CONCLUSIONS: Sazetidine-A significantly reduced
             alcohol and nicotine intake in P rats that self-administer
             higher levels of both drugs. Sazetidine-A may hold promise
             for the treatment of alcohol and nicotine
             addiction.},
   Doi = {10.1007/s00213-010-1878-8},
   Key = {fds274287}
}

@article{fds274285,
   Author = {Rezvani, AH and Sexton, H and Levin, ED},
   Title = {Persistent high alcohol consumption in alcohol-preferring
             (P) rats results from a lack of normal aversion to
             alcohol.},
   Journal = {Alcohol and Alcoholism},
   Volume = {45},
   Number = {3},
   Pages = {219-222},
   Year = {2010},
   Month = {May},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/20356869},
   Abstract = {AIMS: In this study, we tested the impact of pretreatment
             with alcohol on subsequent alcohol drinking in outbred
             Sprague-Dawley and selectively bred alcohol-preferring (P)
             rats. METHODS: As a pretreatment, male Sprague-Dawley and P
             rats were given a passive oral administration of either
             alcohol (1.0 g/kg) or tap water. Then, they were given free
             choice of drinking alcohol (5% v/v) or water in their home
             cages, which was measured over 4 weeks. RESULTS: Without
             alcohol pretreatment, there was no significant strain
             difference in alcohol preference; both strains preferred 5%
             (v/v) alcohol solution. The strain difference was only
             apparent in the groups given alcohol pretreatment. This
             arose from the fact that alcohol pretreatment significantly
             reduced alcohol preference in the Sprague-Dawley rats to a
             level well below 50%, while it did not alter drinking
             behavior in P rats. The same effects were seen with total
             alcohol consumption (g/kg/day). These effects persisted
             throughout the 4 weeks of the study. CONCLUSIONS: The
             principal difference between the Sprague-Dawley and P rats
             was that the P rats did not show the normal aversion to
             alcohol after forced exposure to alcohol that the
             Sprague-Dawley rats showed. One of the potential
             contributors to high alcohol intake and preference in P rats
             may be lack of sensitivity to aversive effects of
             alcohol.},
   Doi = {10.1093/alcalc/agq020},
   Key = {fds274285}
}

@article{fds274288,
   Author = {Adigun, AA and Wrench, N and Levin, ED and Seidler, FJ and Slotkin,
             TA},
   Title = {Neonatal parathion exposure and interactions with a high-fat
             diet in adulthood: Adenylyl cyclase-mediated cell signaling
             in heart, liver and cerebellum.},
   Journal = {Brain Res Bull},
   Volume = {81},
   Number = {6},
   Pages = {605-612},
   Year = {2010},
   Month = {April},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/20074626},
   Abstract = {Organophosphates are developmental neurotoxicants but recent
             evidence points to additional adverse effects on metabolism
             and cardiovascular function. One common mechanism is
             disrupted cell signaling mediated through cyclic AMP,
             targeting neurohumoral receptors, G-proteins and adenylyl
             cyclase (AC) itself. Earlier, we showed that neonatal
             parathion evokes later upregulation of the hepatic AC
             pathway in adolescence but that the effect wanes by young
             adulthood; nevertheless metabolic changes resembling
             prediabetes persist. Here, we administered parathion to
             neonatal rats (postnatal days 1-4, 0.1 or 0.2 mg/kg/day),
             straddling the threshold for cholinesterase inhibition, but
             we extended the studies to much later, 5 months of age. In
             addition, we investigated whether metabolic challenge
             imposed by consuming a high-fat diet for 7 weeks would
             exacerbate neonatal parathion's effects. Parathion alone
             increased the expression or function of G(i), thus reducing
             AC responses to fluoride. Receptors controlling AC activity
             were also affected: beta-adrenergic receptors (betaARs) in
             skeletal muscle were increased, whereas those in the heart
             were decreased, and the latter also showed an elevation of
             m(2)-muscarinic acetylcholine receptors, which inhibit AC.
             The high-fat diet also induced changes in AC signaling,
             enhancing the hepatic AC response to glucagon while
             impairing the cardiac response to fluoride or forskolin, and
             suppressing betaARs and m(2)-muscarinic receptors; the only
             change in the cerebellum was a decrease in betaARs. Although
             there were no significant interactions between neonatal
             parathion exposure and a high-fat diet, their convergent
             effects on the same signaling cascade indicate that early OP
             exposure, separately or combination with dietary factors,
             may contribute to the worldwide increase in the incidence of
             obesity and diabetes.},
   Doi = {10.1016/j.brainresbull.2010.01.003},
   Key = {fds274288}
}

@article{fds274286,
   Author = {Levin, ED and Timofeeva, OA and Yang, L and Petro, A and Ryde, IT and Wrench, N and Seidler, FJ and Slotkin, TA},
   Title = {Early postnatal parathion exposure in rats causes
             sex-selective cognitive impairment and neurotransmitter
             defects which emerge in aging.},
   Journal = {Behav Brain Res},
   Volume = {208},
   Number = {2},
   Pages = {319-327},
   Year = {2010},
   Month = {April},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/20015457},
   Abstract = {Developmental exposure of rats to the organophosphate (OP)
             pesticides leads to altered neurobehavioral function in
             juvenile and young adult stages. The current study was
             conducted to determine whether effects of neonatal parathion
             exposure on cognitive performance persist in older adult and
             aged rats, and the relationship of behavioral changes to
             underlying cholinergic and serotonergic mechanisms. We
             administered parathion to rat pups on postnatal days 1-4, at
             doses spanning the threshold for the initial signs of
             systemic toxicity and for barely detectable cholinesterase
             inhibition (0.1 or 0.2 mg/kg/day). Beginning at 14 months of
             age and continuing until 19 months, the rats were trained in
             the 16-arm radial maze. Controls showed the normal sex
             difference in this spatial learning and memory task, with
             the males committing significantly fewer working memory
             errors than females. Neonatal parathion exposure eliminated
             the sex difference primarily by causing impairment in males.
             In association with the effects on cognitive performance,
             neonatal parathion exposure elicited widespread
             abnormalities in indices of serotonergic (5HT) and
             cholinergic synaptic function, characterized by upregulation
             of 5HT(2) receptors and the 5HT transporter, deficits in
             choline acetyltransferase activity and nicotinic cholinergic
             receptors, and increases in hemicholinium-3 binding to the
             presynaptic choline transporter. Within-animal correlations
             between behavior and neurochemistry indicated a specific
             correlation between working memory performance and
             hippocampal hemicholinium-3 binding; parathion exposure
             eliminated this relationship. Like the behavioral effects,
             males showed greater effects of parathion on neurochemical
             parameters. This study demonstrates the sex-selective,
             long-term behavioral alterations caused by otherwise
             nontoxic neonatal exposure to parathion, with effects
             increasingly expressed with aging.},
   Doi = {10.1016/j.bbr.2009.11.007},
   Key = {fds274286}
}

@article{fds274284,
   Author = {Sanders, D and Simkiss, D and Braddy, D and Baccus, S and Morton, T and Cannady, R and Weaver, N and Rose, JE and Levin, ED},
   Title = {Nicotinic receptors in the habenula: importance for
             memory.},
   Journal = {Neuroscience},
   Volume = {166},
   Number = {2},
   Pages = {386-390},
   Year = {2010},
   Month = {March},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/20034548},
   Abstract = {The habenula is an epithalamic structure through which
             descending connections pass from the telencephalon to the
             brainstem, putting it in a key location to provide feedback
             control over the brainstem monoaminergic projections
             ascending to the telencephalon. Habenular nuclei lesions
             have been shown to impair memory function. The habenular
             nuclei have high concentrations of nicotinic receptors. In
             this study we assessed the role of habenular nicotinic
             receptors for working memory. Adult female Sprague-Dawley
             rats were trained on a 16-arm maze to assess spatial working
             and reference memory. All rats had at least 18 sessions of
             training and then had bilateral chronic infusion cannulae
             placed into the lateral habenula nucleus. These cannulae
             were each connected to a slow delivery osmotic minipump that
             chronically infused mecamylamine 100 microg/side/day (n=9)
             or vehicle (aCSF) for controls (n=15) for a period of 4
             weeks. Both mecamylamine-infused and control rats were
             acutely injected (s.c.) with nicotine (0, 0.2 or 0.4 mg/kg)
             in a repeated measures counterbalanced design twice at each
             dose during the chronic local infusion period. There was a
             significant (P<0.025) mecamylaminexnicotine interaction
             effect on memory performance. Without nicotine injection the
             chronic habenular mecamylamine infusion caused a significant
             (P<0.05) increase in total memory errors. The 0.4 mg/kg
             nicotine dose significantly (P<0.005) reversed the
             mecamylamine-induced memory impairment, returning
             performance back to levels seen in rats with control aCSF
             habenular infusions. The current study determined that
             nicotinic receptors in the lateral habenular nucleus are
             important for spatial memory function. Descending
             projections from the telencephalon through the habenula to
             brainstem nuclei using nicotinic receptors appear to be a
             key pathway for memory processing.},
   Doi = {10.1016/j.neuroscience.2009.12.035},
   Key = {fds274284}
}

@article{fds274282,
   Author = {Levin, ED and Rezvani, AH and Xiao, Y and Slade, S and Cauley, M and Wells,
             C and Hampton, D and Petro, A and Rose, JE and Brown, ML and Paige, MA and McDowell, BE and Kellar, KJ},
   Title = {Sazetidine-A, a selective alpha4beta2 nicotinic receptor
             desensitizing agent and partial agonist, reduces nicotine
             self-administration in rats.},
   Journal = {Journal of Pharmacology and Experimental
             Therapeutics},
   Volume = {332},
   Number = {3},
   Pages = {933-939},
   Year = {2010},
   Month = {March},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/20007754},
   Abstract = {Adequate treatment of tobacco addiction remains problematic.
             Part of the problem with treatment is a poor understanding
             of the pharmacologic aspects of nicotine contributing to
             addiction. In addition to activating nicotinic acetylcholine
             receptors, nicotine also desensitizes them. It is currently
             not known how much of each of nicotine's actions contribute
             to its particular behavioral effects. Sazetidine-A (saz-A)
             is a novel nicotinic receptor-desensitizing agent and
             partial agonist with high selectivity for alpha4beta2
             receptors. The current experiments were conducted to
             determine whether saz-A would reduce nicotine
             self-administration in rats and to characterize its
             ancillary effects. Adult male Sprague-Dawley rats were
             allowed to self-administer nicotine. After initial food
             pellet training followed by 10 sessions of nicotine
             self-administration training, the rats were administered
             saz-A (0.1-3 mg/kg s.c.) or the saline vehicle in a
             repeated-measures counterbalanced design. Saz-A at the 3
             mg/kg dose significantly decreased nicotine
             self-administration relative to performance of the same rats
             after saline injections. In a second study, long-term
             administration of this dose of sazetidine-A over the course
             of 10 sessions significantly reduced nicotine
             self-administration with no apparent diminution of effect.
             Saz-A in this dose range had only modest effects on
             locomotor activity, without any overall decrease in activity
             over a 1-h-long session. Saz-A significantly reduced food
             self-administration, but this effect was smaller than its
             effect on nicotine self-administration. Saz-A, which is a
             selective alpha4beta2-desensitizing agent and partial
             agonist, effectively reduces nicotine self-administration.
             This type of treatment holds promise for a new therapy to
             aid smoking cessation.},
   Doi = {10.1124/jpet.109.162073},
   Key = {fds274282}
}

@article{fds274283,
   Author = {Lassiter, TL and Ryde, IT and Levin, ED and Seidler, FJ and Slotkin,
             TA},
   Title = {Neonatal exposure to parathion alters lipid metabolism in
             adulthood: Interactions with dietary fat intake and
             implications for neurodevelopmental deficits.},
   Journal = {Brain Res Bull},
   Volume = {81},
   Number = {1},
   Pages = {85-91},
   Year = {2010},
   Month = {January},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/19615431},
   Abstract = {Organophosphates are developmental neurotoxicants but recent
             evidence also points to metabolic dysfunction. We determined
             whether neonatal parathion exposure in rats has long-term
             effects on regulation of adipokines and lipid peroxidation.
             We also assessed the interaction of these effects with
             increased fat intake. Rats were given parathion on postnatal
             days 1-4 using doses (0.1 or 0.2mg/kg/day) that straddle the
             threshold for barely detectable cholinesterase inhibition
             and the first signs of systemic toxicity. In adulthood,
             animals were either maintained on standard chow or switched
             to a high-fat diet for 7 weeks. We assessed serum leptin and
             adiponectin, tumor necrosis factor-alpha (TNFalpha) in
             adipose tissues, and thiobarbituric acid reactive species
             (TBARS) in peripheral tissues and brain regions. Neonatal
             parathion exposure uncoupled serum leptin levels from their
             dependence on body weight, suppressed adiponectin and
             elevated TNFalpha in white adipose tissue. Some of the
             effects were offset by a high-fat diet. Parathion reduced
             TBARS in the adipose tissues, skeletal muscle and
             temporal/occipital cortex but not in heart, liver, kidney or
             frontal/parietal cortex; it elevated TBARS in the
             cerebellum; the high-fat diet again reversed many of the
             effects. Neonatal parathion exposure disrupts the regulation
             of adipokines that communicate metabolic status between
             adipose tissues and the brain, while also evoking an
             inflammatory adipose response. Our results are consistent
             with impaired fat utilization and prediabetes, as well as
             exposing a potential relationship between effects on fat
             metabolism and on synaptic function in the
             brain.},
   Doi = {10.1016/j.brainresbull.2009.07.002},
   Key = {fds274283}
}

@article{fds274281,
   Author = {Timofeeva, OA and Eddins, D and Yakel, JL and Blackshear, PJ and Levin,
             ED},
   Title = {Hippocampal infusions of MARCKS peptides impair memory of
             rats on the radial-arm maze.},
   Journal = {Brain Res},
   Volume = {1308},
   Pages = {147-152},
   Year = {2010},
   Month = {January},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/19854162},
   Abstract = {In vitro hippocampal studies by Gay et al. (2008)
             demonstrated that a myristoylated alanine-rich C kinase
             substrate (MARCKS) peptide comprising the phosphorylation
             site or effector domain of the protein acts as a powerful
             inhibitor of alpha7 nicotinic acetylcholine receptors
             (nAChRs), which are known to be critically involved in
             memory function. However, behavioral consequences of
             hippocampal MARCKS peptide infusions have not been
             investigated. The purpose of the current study was to
             determine if local infusions in the rat ventral hippocampus
             of long (comprising amino acids 151-175) and short (amino
             acids 159-165) forms of MARCKS peptides could affect memory
             performance in the 16-arm radial maze. Our results
             demonstrated a dramatic impairment of both working
             (changing) and reference (constant) memory with
             MARCKS(151-175) only. The shorter MARCKS peptide did not
             affect memory performance. This is in line with in vitro
             results reported by Gay et al. (2008) that long, but not
             short, MARCKS peptides inhibit alpha7 nAChRs. We also found
             that the effect of the MARCKS(151-175) peptide was
             dose-dependent, with a robust memory impairment at 10
             microg/side, and smaller inconsistent effects at lower
             doses. Our present behavioral study, together with the
             earlier in vitro study by Gay et al. (2008), suggests that
             effector domain MARCKS peptides could play a significant
             role in memory regulation and impairment.},
   Doi = {10.1016/j.brainres.2009.10.040},
   Key = {fds274281}
}

@article{fds274279,
   Author = {Eddins, D and Cerutti, D and Williams, P and Linney, E and Levin,
             ED},
   Title = {Zebrafish provide a sensitive model of persisting
             neurobehavioral effects of developmental chlorpyrifos
             exposure: comparison with nicotine and pilocarpine effects
             and relationship to dopamine deficits.},
   Journal = {Neurotoxicol Teratol},
   Volume = {32},
   Number = {1},
   Pages = {99-108},
   Year = {2010},
   Month = {January},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/19268529},
   Abstract = {Chlorpyrifos (CPF) an organophosphate pesticide causes
             persisting behavioral dysfunction in rat models when
             exposure is during early development. In earlier work
             zebrafish were used as a complementary model to study
             mechanisms of CPF-induced neurotoxicity induced during early
             development. We found that developmental (first five days
             after fertilization) chlorpyrifos exposure significantly
             impaired learning in zebrafish. However, this testing was
             time and labor intensive. In the current study we tested the
             hypothesis that persisting effects of developmental
             chlorpyrifos could be detected with a brief automated
             assessment of startle response and that this behavioral
             index could be used to help determine the neurobehavioral
             mechanisms for persisting CPF effects. The swimming activity
             of adult zebrafish was assessed by a computerized
             video-tracking device after a sudden tap to the test arena.
             Ten consecutive trials (1/min) were run to determine startle
             response and its habituation. Additionally, habituation
             recovery trials were run at 8, 32 and 128 min after the end
             of the initial trial set. CPF-exposed fish showed a
             significantly (p<0.025) greater overall startle response
             during the 10-trial session compared to controls (group
             sizes: Control N=40, CPF N=24). During the initial recovery
             period (8 min) CPF-exposed fish showed a significantly
             (p<0.01) greater startle response compared to controls. To
             elucidate the contributions of nicotinic and muscarinic
             acetylcholine receptors to developmental CPF-mediated
             effects, the effects of developmental nicotine and
             pilocarpine exposure throughout the first five days after
             fertilization were determined. Developmental nicotine and
             pilocarpine exposure significantly increased startle
             response, though nicotine (group sizes: Control N=32, 15 mM
             N=12, 25 mM N=20) was much more potent than pilocarpine
             (group sizes: Control N=20, 100 microM N=16, 1000 microM
             N=12). Neither was as potent as CPF for developmental
             exposure increasing startle response in adulthood. Lastly,
             developmental CPF exposure decreased dopamine and serotonin
             levels and increased transmitter turnover in developing
             zebrafish larvae (N=4 batches of 50 embryos/treatment). Only
             the decline in dopamine concentrations persisted into
             adulthood (group sizes: Control N=14, CPF N=13). This study
             shows that a quick automated test of startle can detect
             persisting neurobehavioral impairments caused by
             developmental exposure to CPF. This may be helpful in
             screening for persisting neurobehavioral defects from a
             variety of toxicants.},
   Doi = {10.1016/j.ntt.2009.02.005},
   Key = {fds274279}
}

@article{fds274280,
   Author = {Aschner, M and Crofton, KM and Levin, ED},
   Title = {Introduction to the special issue on emerging high
             throughput and complementary model screens for
             neurotoxicology.},
   Journal = {Neurotoxicol Teratol},
   Volume = {32},
   Number = {1},
   Pages = {1-3},
   Year = {2010},
   Month = {January},
   ISSN = {0892-0362},
   url = {http://dx.doi.org/10.1016/j.ntt.2009.08.006},
   Doi = {10.1016/j.ntt.2009.08.006},
   Key = {fds274280}
}

@article{fds274276,
   Author = {Bencan, Z and Sledge, D and Levin, ED},
   Title = {Buspirone, chlordiazepoxide and diazepam effects in a
             zebrafish model of anxiety.},
   Journal = {Pharmacol Biochem Behav},
   Volume = {94},
   Number = {1},
   Pages = {75-80},
   Year = {2009},
   Month = {November},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/19643124},
   Abstract = {Zebrafish are becoming more widely used to study
             neurobehavioral pharmacology. We have developed a method to
             assess novel environment diving behavior of zebrafish as a
             model of stress response and anxiolytic drug effects. In a
             novel tank, zebrafish dwell in the bottom of the tank
             initially and then increase their swimming exploration to
             higher levels over time. We previously found that nicotine,
             which has anxiolytic effects in rodents and humans,
             significantly lessens the novel tank diving response in
             zebrafish. The specificity of the diving effect was
             validated with a novel vs. non-novel test tank. The novel
             tank diving response of zebrafish was tested when given
             three anxiolytic drugs from two different chemical and
             pharmacological classes: buspirone, chlordiazepoxide and
             diazepam. When the test tank was novel the diving response
             was clearly seen whereas it was significantly reduced when
             the test tank was not novel. Buspirone, a serotonergic
             (5HT(1A) receptor agonist) anxiolytic drug with some D(2)
             dopaminergic effect, had a pronounced anxiolytic-like effect
             in the zebrafish diving model at doses that did not have
             sedative effects. In contrast, chlordiazepoxide, a
             benzodiazepine anxiolytic drug, which is an effective
             agonist at GABA-A receptors, did not produce signs of
             anxiolysis in zebrafish over a broad dose range up to those
             that caused sedation. Diazepam another benzodiazepine
             anxiolytic drug did produce an anxiolytic effect at doses
             that did not cause sedation. The zebrafish novel tank diving
             task can be useful in discriminating anxiolytic drugs of
             several classes (serotonergic, benzodiazepines and
             nicotinic).},
   Doi = {10.1016/j.pbb.2009.07.009},
   Key = {fds274276}
}

@article{fds274278,
   Author = {Slotkin, TA and Wrench, N and Ryde, IT and Lassiter, TL and Levin, ED and Seidler, FJ},
   Title = {Neonatal parathion exposure disrupts serotonin and dopamine
             synaptic function in rat brain regions: modulation by a
             high-fat diet in adulthood.},
   Journal = {Neurotoxicol Teratol},
   Volume = {31},
   Number = {6},
   Pages = {390-399},
   Year = {2009},
   Month = {November},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/19616088},
   Abstract = {The consequences of exposure to developmental neurotoxicants
             are influenced by environmental factors. In the present
             study, we examined the role of dietary fat intake. We
             administered parathion to neonatal rats and then evaluated
             whether a high-fat diet begun in adulthood could modulate
             the persistent effects on 5HT and DA systems. Neonatal rats
             received parathion on postnatal days 1-4 at 0.1 or 0.2
             mg/kg/day, straddling the cholinesterase inhibition
             threshold. In adulthood, half the animals in each exposure
             group were given a high-fat diet for 8 weeks. We assessed
             5HT and DA concentrations and turnover in brain regions
             containing their respective cell bodies and projections. In
             addition, we monitored 5HT1A and 5HT2 receptor binding and
             the concentration of 5HT presynaptic transporters. Neonatal
             parathion exposure evoked widespread increases in
             neurotransmitter turnover, indicative of presynaptic
             hyperactivity, further augmented by 5HT receptor
             upregulation. In control rats, consumption of a high-fat
             diet recapitulated many of the changes seen with neonatal
             parathion exposure; the effects represented convergent
             mechanisms, since the high-fat diet often obtunded further
             increases caused by parathion. Neonatal parathion exposure
             causes lasting hyperactivity of 5HT and DA systems
             accompanied by 5HT receptor upregulation, consistent with
             "miswiring" of neuronal projections. A high-fat diet obtunds
             the effect of parathion, in part by eliciting similar
             changes itself. Thus, dietary factors may produce similar
             synaptic changes as do developmental neurotoxicants,
             potentially contributing to the increasing incidence of
             neurodevelopmental disorders.},
   Doi = {10.1016/j.ntt.2009.07.003},
   Key = {fds274278}
}

@article{fds274277,
   Author = {Cannady, R and Weir, R and Wee, B and Gotschlich, E and Kolia, N and Lau,
             E and Brotherton, J and Levin, ED},
   Title = {Nicotinic antagonist effects in the mediodorsal thalamic
             nucleus: regional heterogeneity of nicotinic receptor
             involvement in cognitive function.},
   Journal = {Biochem Pharmacol},
   Volume = {78},
   Number = {7},
   Pages = {788-794},
   Year = {2009},
   Month = {October},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/19477167},
   Abstract = {Nicotine has been found in many studies to improve cognitive
             function. However, some studies have not found this effect
             and others have seen nicotine-induced impairments. Systemic
             administration bathes the brain with drugs. However, the
             brain is quite intricately organized with various regions
             playing very different roles in the bases of cognitive
             function. We have examined the role of nicotinic receptors
             in a variety of brain areas for memory. In the hippocampus
             and amygdala, local infusions of both alpha7 and alpha4beta2
             antagonists methyllyaconitine (MLA) and dihydro-beta-erythroidine
             (DHbetaE) significantly impair memory. In the current
             studies we locally infused acute and chronic doses of MLA
             and DHbetaE into the mediodorsal thalamic nucleus and tested
             memory function on a 16-arm radial maze. The rats also
             received systemic nicotine to determine the impact of more
             generalized nicotine effects. Since nicotinic treatments are
             being developed for cognitive impairment of schizophrenia,
             interactions were studied with the antipsychotic drug
             clozapine. In the acute study, the 6.75 microg/side of
             DHbetaE improved working memory. Co-administration of MLA
             reversed the DHbetaE-induced improvement. Chronic DHbetaE
             infusions into the mediodorsal thalamic nucleus also
             improved working memory. Systemic nicotine reversed this
             effect. Clozapine had no significant interaction. Nicotinic
             alpha4beta2 receptors in the mediodorsal thalamic nucleus
             appear to play an opposite role with regard to working
             memory than those in the hippocampus and amygdala.
             Heterogeneity in response to nicotinic drugs given
             systemically may be due to anatomically distinct nicotinic
             systems in the brain and their unique roles in the neural
             bases of cognitive function.},
   Doi = {10.1016/j.bcp.2009.05.021},
   Key = {fds274277}
}

@article{fds274322,
   Author = {Schramm-Sapyta, NL and Walker, QD and Caster, JM and Levin, ED and Kuhn,
             CM},
   Title = {Are adolescents more vulnerable to drug addiction than
             adults? Evidence from animal models.},
   Journal = {Psychopharmacology (Berl)},
   Volume = {206},
   Number = {1},
   Pages = {1-21},
   Year = {2009},
   Month = {September},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/19547960},
   Abstract = {BACKGROUND AND RATIONALE: Epidemiological evidence suggests
             that people who begin experimenting with drugs of abuse
             during early adolescence are more likely to develop
             substance use disorders (SUDs), but this correlation does
             not guarantee causation. Animal models, in which age of
             onset can be tightly controlled, offer a platform for
             testing causality. Many animal models address drug effects
             that might promote or discourage drug intake and
             drug-induced neuroplasticity. METHODS: We have reviewed the
             preclinical literature to investigate whether adolescent
             rodents are differentially sensitive to rewarding,
             reinforcing, aversive, locomotor, and withdrawal-induced
             effects of drugs of abuse. RESULTS AND CONCLUSIONS: The
             rodent model literature consistently suggests that the
             balance of rewarding and aversive effects of drugs of abuse
             is tipped toward reward in adolescence. However, increased
             reward does not consistently lead to increased voluntary
             intake: age effects on voluntary intake are drug and method
             specific. On the other hand, adolescents are consistently
             less sensitive to withdrawal effects, which could protect
             against compulsive drug seeking. Studies examining neuronal
             function have revealed several age-related effects but have
             yet to link these effects to vulnerability to SUDs. Taken
             together, the findings suggest factors which may promote
             recreational drug use in adolescents, but evidence relating
             to pathological drug-seeking behavior is lacking. A call is
             made for future studies to address this gap using behavioral
             models of pathological drug seeking and for neurobiologic
             studies to more directly link age effects to SUD
             vulnerability.},
   Doi = {10.1007/s00213-009-1585-5},
   Key = {fds274322}
}

@article{fds274325,
   Author = {Levin, ED and Aschner, M and Heberlein, U and Ruden, D and Welsh-Bohmer,
             KA and Bartlett, S and Berger, K and Chen, L and Corl, AB and Eddins, D and French, R and Hayden, KM and Helmcke, K and Hirsch, HVB and Linney, E and Lnenicka, G and Page, GP and Possidente, D and Possidente, B and Kirshner, A},
   Title = {Genetic aspects of behavioral neurotoxicology.},
   Journal = {Neurotoxicology},
   Volume = {30},
   Number = {5},
   Pages = {741-753},
   Year = {2009},
   Month = {September},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/19647018},
   Abstract = {Considerable progress has been made over the past couple of
             decades concerning the molecular bases of neurobehavioral
             function and dysfunction. The field of neurobehavioral
             genetics is becoming mature. Genetic factors contributing to
             neurologic diseases such as Alzheimer's disease have been
             found and evidence for genetic factors contributing to other
             diseases such as schizophrenia and autism are likely. This
             genetic approach can also benefit the field of behavioral
             neurotoxicology. It is clear that there is substantial
             heterogeneity of response with behavioral impairments
             resulting from neurotoxicants. Many factors contribute to
             differential sensitivity, but it is likely that genetic
             variability plays a prominent role. Important discoveries
             concerning genetics and behavioral neurotoxicity are being
             made on a broad front from work with invertebrate and
             piscine mutant models to classic mouse knockout models and
             human epidemiologic studies of polymorphisms. Discovering
             genetic factors of susceptibility to neurobehavioral
             toxicity not only helps identify those at special risk, it
             also advances our understanding of the mechanisms by which
             toxicants impair neurobehavioral function in the larger
             population. This symposium organized by Edward Levin and
             Annette Kirshner, brought together researchers from the
             laboratories of Michael Aschner, Douglas Ruden, Ulrike
             Heberlein, Edward Levin and Kathleen Welsh-Bohmer conducting
             studies with Caenorhabditis elegans, Drosophila, fish,
             rodents and humans studies to determine the role of genetic
             factors in susceptibility to behavioral impairment from
             neurotoxic exposure.},
   Doi = {10.1016/j.neuro.2009.07.014},
   Key = {fds274325}
}

@article{fds274274,
   Author = {Noyes, PD and McElwee, MK and Miller, HD and Clark, BW and Van Tiem and LA and Walcott, KC and Erwin, KN and Levin, ED},
   Title = {The toxicology of climate change: environmental contaminants
             in a warming world.},
   Journal = {Environ Int},
   Volume = {35},
   Number = {6},
   Pages = {971-986},
   Year = {2009},
   Month = {August},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/19375165},
   Abstract = {Climate change induced by anthropogenic warming of the
             earth's atmosphere is a daunting problem. This review
             examines one of the consequences of climate change that has
             only recently attracted attention: namely, the effects of
             climate change on the environmental distribution and
             toxicity of chemical pollutants. A review was undertaken of
             the scientific literature (original research articles,
             reviews, government and intergovernmental reports) focusing
             on the interactions of toxicants with the environmental
             parameters, temperature, precipitation, and salinity, as
             altered by climate change. Three broad classes of chemical
             toxicants of global significance were the focus: air
             pollutants, persistent organic pollutants (POPs), including
             some organochlorine pesticides, and other classes of
             pesticides. Generally, increases in temperature will enhance
             the toxicity of contaminants and increase concentrations of
             tropospheric ozone regionally, but will also likely increase
             rates of chemical degradation. While further research is
             needed, climate change coupled with air pollutant exposures
             may have potentially serious adverse consequences for human
             health in urban and polluted regions. Climate change
             producing alterations in: food webs, lipid dynamics, ice and
             snow melt, and organic carbon cycling could result in
             increased POP levels in water, soil, and biota. There is
             also compelling evidence that increasing temperatures could
             be deleterious to pollutant-exposed wildlife. For example,
             elevated water temperatures may alter the biotransformation
             of contaminants to more bioactive metabolites and impair
             homeostasis. The complex interactions between climate change
             and pollutants may be particularly problematic for species
             living at the edge of their physiological tolerance range
             where acclimation capacity may be limited. In addition to
             temperature increases, regional precipitation patterns are
             projected to be altered with climate change. Regions subject
             to decreases in precipitation may experience enhanced
             volatilization of POPs and pesticides to the atmosphere.
             Reduced precipitation will also increase air pollution in
             urbanized regions resulting in negative health effects,
             which may be exacerbated by temperature increases. Regions
             subject to increased precipitation will have lower levels of
             air pollution, but will likely experience enhanced surface
             deposition of airborne POPs and increased run-off of
             pesticides. Moreover, increases in the intensity and
             frequency of storm events linked to climate change could
             lead to more severe episodes of chemical contamination of
             water bodies and surrounding watersheds. Changes in salinity
             may affect aquatic organisms as an independent stressor as
             well as by altering the bioavailability and in some
             instances increasing the toxicity of chemicals. A paramount
             issue will be to identify species and populations especially
             vulnerable to climate-pollutant interactions, in the context
             of the many other physical, chemical, and biological
             stressors that will be altered with climate change.
             Moreover, it will be important to predict tipping points
             that might trigger or accelerate synergistic interactions
             between climate change and contaminant exposures.},
   Doi = {10.1016/j.envint.2009.02.006},
   Key = {fds274274}
}

@article{fds274275,
   Author = {Rezvani, AH and Overstreet, DH and Vaidya, AH and Zhao, B and Levin,
             ED},
   Title = {Carisbamate, a novel antiepileptic candidate compound,
             attenuates alcohol intake in alcohol-preferring
             rats.},
   Journal = {Alcohol Clin Exp Res},
   Volume = {33},
   Number = {8},
   Pages = {1366-1373},
   Year = {2009},
   Month = {August},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/19413647},
   Abstract = {BACKGROUND: Since 1994, when naltrexone (Revia) was approved
             by the FDA for the treatment of alcoholism, only 2 other
             drugs (Campral and Topamax have been approved for alcoholism
             treatment. However, various experimental drugs, including
             antiepileptic medications, have been tested in both animal
             models and in humans with some promising results. The
             purpose of this project was to study the effect of the novel
             neuromodulator carisbamate, which is in development for
             epilepsy treatment, on alcohol intake in selectively bred
             alcohol-preferring rats. METHODS: Male alcohol-preferring
             inbred P rats were allowed to freely drink water or alcohol
             (10%, v/v) using a 2-bottle choice procedure. After stable
             baselines for alcohol and water intakes were established,
             the acute effects of oral carisbamate (0, 10, 30, 45, 60,
             and 90 mg/kg) were assessed. Then, the chronic effect of the
             compound (60 mg/kg/day for 14 consecutive days) on alcohol
             intake was assessed in a separate group of male P rats. In
             another set of experiments, the effects of carisbamate and
             naltrexone on alcohol withdrawal-induced elevated drinking
             of alcohol, an index of craving, were compared. Rats were
             withdrawn from alcohol for 24 hours and were given vehicle,
             20 mg/kg naltrexone or 60 mg/kg carisbamate 30 minutes
             before re-exposure to alcohol. Alcohol and water intake was
             measured 6 hours after alcohol re-exposure. To determine the
             effects of carisbamate on saccharin preference, rats were
             put on a 2-bottle choice of water versus a solution of 2%
             saccharin. Then, the effect of the highest dose of
             carisbamate (90 mg/kg) and naltrexone (20 mg/kg) and the
             vehicle on saccharin preference was determined. RESULTS: Our
             results showed that there was a selective dose-dependent
             reduction in alcohol intake and preference in the
             alcohol-preferring P rat after an acute oral administration
             of carisbamate. There were no significant effects on food or
             water intake. Chronic administration of carisbamate
             significantly reduced alcohol intake and preference
             initially, but partial tolerance developed after the 10th
             treatment. The degree of tolerance development was less than
             that observed for naltrexone. Acute administration of
             carisbamate was more effective than naltrexone in reducing
             enhanced alcohol intake after a period of alcohol
             deprivation. Compared with control vehicle neither
             carisbamate nor naltrexone had a significant effect on
             saccharin intake and preference. CONCLUSION: The novel
             neuromodulator compound carisbamate has a favorable profile
             of effects on alcohol intake and related measures and should
             be considered for testing on human alcoholics.},
   Doi = {10.1111/j.1530-0277.2009.00966.x},
   Key = {fds274275}
}

@article{fds274268,
   Author = {Slotkin, TA and Lassiter, TL and Ryde, IT and Wrench, N and Levin, ED and Seidler, FJ},
   Title = {Consumption of a high-fat diet in adulthood ameliorates the
             effects of neonatal parathion exposure on acetylcholine
             systems in rat brain regions.},
   Journal = {Environ Health Perspect},
   Volume = {117},
   Number = {6},
   Pages = {916-922},
   Year = {2009},
   Month = {June},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/19590683},
   Abstract = {BACKGROUND: Developmental exposure to a wide variety of
             developmental neurotoxicants, including organophosphate
             pesticides, evokes late-emerging and persistent
             abnormalities in acetylcholine (ACh) systems. We are seeking
             interventions that can ameliorate or reverse the effects
             later in life. OBJECTIVES: We administered parathion to
             neonatal rats and then evaluated whether a high-fat diet
             begun in adulthood could reverse the effects on ACh systems.
             METHODS: Neonatal rats received parathion on postnatal days
             1-4 at 0.1 or 0.2 mg/kg/day, straddling the cholinesterase
             inhibition threshold. In adulthood, half the animals were
             switched to a high-fat diet for 8 weeks. We assessed three
             indices of ACh synaptic function: nicotinic ACh receptor
             binding, choline acetyltransferase activity, and
             hemicholinium-3 binding. Determinations were performed in
             brain regions comprising all the major ACh projections and
             cell bodies. RESULTS: Neonatal parathion exposure evoked
             widespread abnormalities in ACh synaptic markers,
             encompassing effects in brain regions possessing ACh
             projections and ACh cell bodies. In general, males were
             affected more than females. Of 17 regional ACh marker
             abnormalities (10 male, 7 female), 15 were reversed by the
             high-fat diet. CONCLUSIONS: A high-fat diet reverses
             neurodevelopmental effects of neonatal parathion exposure on
             ACh systems. This points to the potential for
             nonpharmacologic interventions to offset the effects of
             developmental neurotoxicants. Further, cryptic
             neurodevelopmental deficits evoked by environmental
             exposures may thus engender a later preference for a
             high-fat diet to maintain normal ACh function, ultimately
             contributing to obesity.},
   Doi = {10.1289/ehp.0800459},
   Key = {fds274268}
}

@article{fds274324,
   Author = {Eddins, D and Klein, RC and Yakel, JL and Levin, ED},
   Title = {Hippocampal infusions of apolipoprotein E peptides induce
             long-lasting cognitive impairment.},
   Journal = {Brain Res Bull},
   Volume = {79},
   Number = {2},
   Pages = {111-115},
   Year = {2009},
   Month = {April},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/19185602},
   Abstract = {The inheritance of the varepsilon4 allele of apolipoprotein
             E (ApoE4) and cholinergic system dysfunction have long been
             associated with the pathology of Alzheimer's disease (AD).
             Recently, in vitro studies have established a direct link
             between ApoE and cholinergic function in that synthetic
             peptides containing segments of the ApoE protein
             (ApoE(133-149) and ApoE(141-148)) interact with alpha7
             nicotinic acetylcholine receptors (nAChRs) in the
             hippocampus. This raises the possibility that ApoE peptides
             may contribute to cognitive impairment in AD in that the
             hippocampus plays a key role in cognitive functioning. To
             test this, we acutely infused ApoE peptides into the ventral
             hippocampus of female Sprague-Dawley rats and assessed the
             resultant effects on radial-arm maze choice accuracy over a
             period of weeks after the infusion. Local ventral
             hippocampal infusion of ApoE peptides caused significant
             cognitive impairment in radial-arm maze learning that
             persisted several weeks after the acute infusion. This
             persisting deficit may be an important model for
             understanding the relationship between ApoE protein-induced
             neurotoxicity and cognitive impairment as well as serve as a
             platform for the development of new therapies to avoid
             neurotoxicity and cognitive decline.},
   Doi = {10.1016/j.brainresbull.2009.01.003},
   Key = {fds274324}
}

@article{fds274272,
   Author = {Rezvani, AH and Kholdebarin, E and Brucato, FH and Callahan, PM and Lowe, DA and Levin, ED},
   Title = {Effect of R3487/MEM3454, a novel nicotinic alpha7 receptor
             partial agonist and 5-HT3 antagonist on sustained attention
             in rats.},
   Journal = {Progress in Neuro Psychopharmacology & Biological
             Psychiatry},
   Volume = {33},
   Number = {2},
   Pages = {269-275},
   Year = {2009},
   Month = {March},
   ISSN = {0278-5846},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/19110025},
   Abstract = {It is well established that nicotinic systems in the brain
             are critically involved in attentional processes in both
             animals and humans. The current study assessed the effects
             of a novel nicotinic alpha7 receptor partial agonist and
             5-HT3 antagonist, R3487/MEM3454 (also referred to as R3487
             or MEM 3454) on sustained attention in rats performing an
             operant visual signal detection task. The effects of
             R3487/MEM3454 were compared to those of the
             acetylcholinesterase inhibitor/nicotinic alpha7 allosteric
             positive modulator galanthamine. Adult female Sprague-Dawley
             rats were injected subcutaneously with R3487/MEM3454 (0.03,
             0.1, 0.15, 0.3 and 0.6 mg/kg), galanthamine (0.25, 0.5, 1, 2
             mg/kg) or vehicle 30 min before the attentional test. In the
             second study, the time-dependent effects of R3487/MEM3454
             were assessed by injecting the compound (0.6 mg/kg, s.c.) at
             different pretreatment intervals (30, 60 or 90 min) before
             the start of the attentional task. Our results show a
             significant dose-effect for R3487/MEM3454 on percent hit
             accuracy performance without any significant alteration on
             percent correct rejection performance. In the time-dependent
             test, R3487/MEM3454 significantly increased the percent hit
             accuracy performance when animals were injected 60 min
             before the start of the attentional task. Administration of
             galanthamine failed to significantly increase percent hit
             accuracy performance and increasing the dose of galanthamine
             produced a decrease in percent correct rejection
             performance. The present findings with R3487/MEM3454 suggest
             that nicotinic alpha7 receptors and/or 5-HT3 receptors may
             play an important role in modulating sustained attention and
             that R3487/MEM3454 may have therapeutic potential in
             improving sustained attention in humans.},
   Doi = {10.1016/j.pnpbp.2008.11.018},
   Key = {fds274272}
}

@article{fds274273,
   Author = {Levin, ED and Perkins, A and Brotherton, T and Qazi, M and Berez, C and Montalvo-Ortiz, J and Davis, K and Williams, P and Christopher,
             NC},
   Title = {Chronic underactivity of medial frontal cortical
             beta2-containing nicotinic receptors increases
             clozapine-induced working memory impairment in female
             rats.},
   Journal = {Progress in Neuro Psychopharmacology & Biological
             Psychiatry},
   Volume = {33},
   Number = {2},
   Pages = {296-302},
   Year = {2009},
   Month = {March},
   ISSN = {0278-5846},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/19146909},
   Abstract = {Nicotinic receptor decreases in the frontal cortex and
             hippocampus are important mediators of cognitive impairment
             in both schizophrenia and Alzheimer's disease. Drug
             treatments for these diseases should take into account the
             impacts of compromised brain function on drug response. This
             study investigated the impact of compromised nicotinic
             receptor activity in the frontal cortex in rats on memory
             function. Since both Alzheimer's disease and schizophrenia
             can involve psychosis, antipsychotic drugs are often given.
             The impacts of antipsychotic drugs on cognitive function
             have been found to be quite variable. It is the hypothesis
             of this and previous studies that the cognitive effects of
             antispychotic drugs on cognitive function depend on the
             integrity of brain systems involved in cognition. Previously
             in studies of the hippocampus, we found that chronic
             inhibition of beta2-containing nicotinic receptors with
             dihydro-beta-erythrodine (DHbetaE) impaired working memory
             and that this effect was attenuated by the antipsychotic
             drug clozapine. In contrast, chronic hippocampal alpha7
             nicotinic receptor blockade with methyllycaconitine (MLA)
             potentiated the clozapine-induced memory impairment which is
             seen in rats without compromised nicotinic receptor
             activity. The current study determined medial frontal
             cortical alpha7 and beta2-containing nicotinic receptor
             involvement in memory and the interactions with
             antipsychotic drug therapy with clozapine. Chronic DHbetaE
             and MLA infusion effects and interactions with systemic
             clozapine were assessed in female rats tested for memory on
             the radial-arm maze. Antipsychotic drug interactions with
             chronic systemic nicotine were investigated because
             nicotinic procognitive treatment has been proposed. The same
             local infusion DHbetaE dose that impaired memory with
             hippocampal infusion did not impair memory when infused in
             the medial frontal cortex. Frontal DHbetaE infusion
             potentiated clozapine-induced memory impairment, whereas
             previously the memory impairment caused by hippocampal
             DHbetaE infusion was attenuated by clozapine. Frontal
             cortical MLA infusions at a dose that previously was found
             to potentiate the clozapine-induced memory impairment with
             hippocampal infusion had no significant effect when infused
             into the medial frontal cortex. The location and subtype of
             nicotinic receptor underactivity are critical determinates
             for clozapine effects on memory. Patients with hippocampal
             beta2-containing nicotinic receptor loss may be well treated
             with clozapine therapy, while those with frontal cortical
             beta2-containing receptor loss may have a potentiated memory
             impairment caused by clozapine.},
   Doi = {10.1016/j.pnpbp.2008.12.003},
   Key = {fds274273}
}

@article{fds274271,
   Author = {Rezvani, AH and Kholdebarin, E and Cauley, MC and Dawson, E and Levin,
             ED},
   Title = {Attenuation of pharmacologically-induced attentional
             impairment by methylphenidate in rats.},
   Journal = {Pharmacology, Biochemistry, and Behavior},
   Volume = {92},
   Number = {1},
   Pages = {141-146},
   Year = {2009},
   Month = {March},
   ISSN = {0091-3057},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/19041337},
   Abstract = {Methylphenidate is widely used as a treatment option for
             attention deficit hyperactivity disorder. In animal models
             of attentional impairment, it is an important validation to
             determine whether this clinically effective treatment
             attenuates deficits. The purpose of the current study was to
             determine whether methylphenidate can diminish attentional
             impairment induced by three pharmacological agents with
             different mechanisms of action: scopolamine, mecamylamine,
             and dizocilpine. Female rats were trained on an operant
             visual signal detection task. Ten min before the test, the
             rats were injected subcutaneously with methylphenidate (0,
             0.1, 0.3 mg/kg), scopolamine (0, 0.005, 0.01 mg/kg),
             mecamylamine (0, 2, 4 mg/kg), dizocilpine (0, 0.025, 0.05
             mg/kg) or combinations of methylphenidate with these drugs.
             In each of the experiments, all rats received every
             treatment in a repeated measures counterbalanced order.
             Correction rejection accuracy was impaired by all three of
             the antagonists and these effects were attenuated by
             methylphenidate. Both scopolamine at 0.01 and dizocilpine at
             0.05 mg/kg significantly impaired percent correct rejection
             choice accuracy, an effect that was ameliorated by
             methylphenidate. Mecamylamine (4 mg/kg) impaired attentional
             performance by reducing percent hit and percent correct
             rejection. Co-administration of methylphenidate failed to
             significantly affect the mecamylamine-induced attentional
             impairment. Methylphenidate alone at 0.3 mg/kg significantly
             improved percent hit choice accuracy only in low-performing
             rats in one experiment, an effect which was reversed by
             scopolamine. These data show that methylphenidate
             effectively reverses the attentional impairment caused by
             scopolamine and dizocilpine. These findings further validate
             the operant visual signal detection task for assessing
             attentional impairments and their reversal.},
   Doi = {10.1016/j.pbb.2008.11.005},
   Key = {fds274271}
}

@article{fds274269,
   Author = {Schmajuk, NA and Larrauri, JA and De la Casa and LG and Levin,
             ED},
   Title = {Attenuation of auditory startle and prepulse inhibition by
             unexpected changes in ambient illumination through
             dopaminergic mechanisms.},
   Journal = {Behav Brain Res},
   Volume = {197},
   Number = {2},
   Pages = {251-261},
   Year = {2009},
   Month = {February},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/18801390},
   Abstract = {We investigated the role of dopaminergic mechanisms in the
             attenuation of the acoustic startle response and prepulse
             inhibition (PPI) in rats by the introduction of unexpected
             changes in environment illumination. Experiment 1 showed
             that Dark-to-Light transitions robustly reduce startle
             responses and PPI. Experiment 2 showed that this phenomenon
             habituates across repeated testing sessions and reappears
             after an interval without testing. Experiment 3 demonstrated
             that haloperidol blocks the startle and PPI-reducing effect
             of the Dark-to-Light transition. We show how a computational
             model of acoustic startle response and prepulse inhibition
             can be extended to incorporate the empirical effects
             demonstrated in this study. We conclude that sensory gating
             as measured by prepulse inhibition is markedly attenuated in
             situations where novel stimuli are introduced during a test
             session and that dopaminergic systems may be involved in the
             dynamic changes evoked by the onset of illumination.},
   Doi = {10.1016/j.bbr.2008.08.030},
   Key = {fds274269}
}

@article{fds274270,
   Author = {Levin, ED and Petro, A and Rezvani, AH and Pollard, N and Christopher,
             NC and Strauss, M and Avery, J and Nicholson, J and Rose,
             JE},
   Title = {Nicotinic alpha7- or beta2-containing receptor knockout:
             effects on radial-arm maze learning and long-term nicotine
             consumption in mice.},
   Journal = {Behav Brain Res},
   Volume = {196},
   Number = {2},
   Pages = {207-213},
   Year = {2009},
   Month = {January},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/18831991},
   Abstract = {Classically, it has been thought that high-affinity
             nicotinic receptors-containing beta2 subunits are the most
             important receptor subtypes for nicotinic involvement in
             cognitive function and nicotine self-administration, while
             low affinity alpha7-containing nicotinic receptors have not
             been thought to be important. In the current study, we found
             that knockout of either beta2 or alpha7 subunits caused
             significant deficits in spatial discrimination in mice. The
             character of the impairment in the two knockouts was
             different. The beta2 knockout preferentially impaired
             cognition in males while the alpha7 caused impairment
             regardless of sex. Both beta2- and alpha7-containing
             nicotinic receptors also are important for nicotine
             self-administration, also in different ways. Most animal
             model studies of nicotine self-administration are relatively
             short-term whereas the problem of tobacco addiction is
             considerably longer-term. To better model the impact of
             nicotinic receptor subtypes on nicotine self-administration
             over the long-term, we studied the impact of genetic
             knockout of low affinity alpha7 receptors vs. high-affinity
             beta2-containing nicotinic receptors. Mice with knockouts of
             either of these receptors and their wildtype counter parts
             were given free access to a choice of nicotine-containing
             and nicotine-free solution in their home cages on a
             continuous basis over a period of 5 months. During the first
             few weeks, the beta2-containing nicotinic receptor knockout
             mice showed a significant decrease in nicotine consumption
             relative to wildtype mice, whereas the alpha7 knockout mice
             did not significantly differ from wildtype controls at the
             beginning of their access to nicotine. Interestingly, in the
             longer-term after the first few weeks of nicotine access,
             the beta2 knockout mice returned to wildtype mouse levels of
             nicotine consumption, whereas the alpha7 knockout mice
             developed an emergent decrease in nicotine consumption. The
             alpha7 receptor knockout-induced decrease in nicotine
             consumption persisted for the 5-month period of the study.
             Both alpha7- and beta2-containing nicotinic receptors play
             critical roles in cognitive function and nicotine
             self-administration. Regarding cognitive function,
             beta2-containing receptors are important for maintaining
             normal sex differences in spatial learning and memory,
             whereas alpha7 receptors are important for cognitive
             function regardless of sex. Regarding nicotine
             self-administration high-affinity beta2-containing nicotinic
             receptors are important for consumption during the initial
             phase of nicotine access, but it is the alpha7 nicotinic
             receptors that are important for the longer-term regulation
             of nicotine consumption.},
   Doi = {10.1016/j.bbr.2008.08.048},
   Key = {fds274270}
}

@article{fds274265,
   Author = {Eddins, D and Petro, A and Williams, P and Cerutti, DT and Levin,
             ED},
   Title = {Nicotine effects on learning in zebrafish: the role of
             dopaminergic systems.},
   Journal = {Psychopharmacology (Berl)},
   Volume = {202},
   Number = {1-3},
   Pages = {103-109},
   Year = {2009},
   Month = {January},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/18716760},
   Abstract = {RATIONALE: Nicotine improves cognitive function in a number
             of animal models including rats, mice, monkeys, and
             recently, zebrafish. The zebrafish model allows higher
             throughput and ease in discovering mechanisms of cognitive
             improvement. MATERIALS AND METHODS: To further characterize
             the neural bases of nicotine effects on learning in
             zebrafish, we determined changes in dopaminergic systems
             that accompany nicotine-enhanced learning. RESULTS: Nicotine
             improved learning and increased brain levels of
             dihydroxyphenylacetic acid (DOPAC), the primary dopamine
             metabolite. There was a significant correlation between
             choice accuracy and DOPAC levels. The nicotinic antagonist
             mecamylamine blocked the nicotine-induced increase in DOPAC
             concentrations, in line with our previous finding that
             mecamylamine reversed nicotine-induced learning improvement.
             CONCLUSIONS: Dopamine systems are related to learning in
             zebrafish; nicotine exposure increases both learning rates
             and DOPAC levels; and nicotinic antagonist administration
             blocks nicotine-induced rises in DOPAC concentrations. Rapid
             cognitive assessment of drugs with zebrafish could serve as
             a useful screening tool for the development of new
             therapeutics for cognitive dysfunction.},
   Doi = {10.1007/s00213-008-1287-4},
   Key = {fds274265}
}

@article{fds274267,
   Author = {Slotkin, TA and Levin, ED and Seidler, FJ},
   Title = {Developmental neurotoxicity of parathion: progressive
             effects on serotonergic systems in adolescence and
             adulthood.},
   Journal = {Neurotoxicology and Teratology},
   Volume = {31},
   Number = {1},
   Pages = {11-17},
   Year = {2009},
   Month = {January},
   ISSN = {0892-0362},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/18773955},
   Abstract = {Neonatal exposures to organophosphates that are not acutely
             symptomatic or that produce little or no cholinesterase
             inhibition can nevertheless compromise the development and
             later function of critical neural pathways, including
             serotonin (5HT) systems that regulate emotional behaviors.
             We administered parathion to newborn rats on postnatal days
             (PN) 1-4 at doses spanning the threshold for detectable
             cholinesterase inhibition (0.1 mg/kg/day) and the first
             signs of loss of viability (0.2 mg/kg/day). In adolescence
             (PN30), young adulthood (PN60) and full adulthood (PN100),
             we measured radioligand binding to 5HT(1A) and 5HT(2)
             receptors, and to the 5HT transporter in the brain regions
             comprising all the major 5HT projections and 5HT cell
             bodies. Parathion caused a biphasic effect over later
             development with initial, widespread upregulation of 5HT(1A)
             receptors that peaked in the frontal/parietal cortex by
             PN60, followed by a diminution of that effect in most
             regions and emergence of deficits at PN100. There were
             smaller, but statistically significant changes in 5HT(2)
             receptors and the 5HT transporter. These findings stand in
             strong contrast to previous results with neonatal exposure
             to a different organophosphate, chlorpyrifos, which evoked
             parallel upregulation of all three 5HT synaptic proteins
             that persisted from adolescence through full adulthood and
             that targeted males much more than females. Our results
             support the view that the various organophosphates have
             disparate effects on 5HT systems, distinct from their shared
             property as cholinesterase inhibitors, and the targeting of
             5HT function points toward the importance of studying the
             impact of these agents on 5HT-linked behaviors.},
   Doi = {10.1016/j.ntt.2008.08.004},
   Key = {fds274267}
}

@article{fds274266,
   Author = {Timofeeva, OA and Sanders, D and Seemann, K and Yang, L and Hermanson,
             D and Regenbogen, S and Agoos, S and Kallepalli, A and Rastogi, A and Braddy, D and Wells, C and Perraut, C and Seidler, FJ and Slotkin, TA and Levin, ED},
   Title = {Persistent behavioral alterations in rats neonatally exposed
             to low doses of the organophosphate pesticide,
             parathion.},
   Journal = {Brain Res Bull},
   Volume = {77},
   Number = {6},
   Pages = {404-411},
   Year = {2008},
   Month = {December},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/18817854},
   Abstract = {Although developmental exposures of rats to low levels of
             the organophosphate pesticides (OPs), chlorpyrifos (CPF) or
             diazinon (DZN), both cause persistent neurobehavioral
             effects, there are important differences in their
             neurotoxicity. The current study extended investigation to
             parathion (PTN), an OP that has higher systemic toxicity
             than either CPF or DZN. We gave PTN on postnatal days (PND)
             1-4 at doses spanning the threshold for systemic toxicity
             (0, 0.1 or 0.2 mg/kg/day, s.c.) and performed a battery of
             emotional and cognitive behavioral tests in adolescence
             through adulthood. The higher PTN dose increased time spent
             on the open arms and the number of center crossings in the
             plus maze, indicating greater risk-taking and overall
             activity. This group also showed a decrease in tactile
             startle response without altering prepulse inhibition,
             indicating a blunted acute sensorimotor reaction without
             alteration in sensorimotor plasticity. T-maze spontaneous
             alternation, novelty-suppressed feeding, preference for
             sweetened chocolate milk, and locomotor activity were not
             significantly affected by neonatal PTN exposure. During
             radial-arm maze acquisition, rats given the lower PTN dose
             committed fewer errors compared to controls and displayed
             lower sensitivity to the amnestic effects of the NMDA
             receptor blocker, dizocilpine. No PTN effects were observed
             with regard to the sensitivity to blockade of muscarinic and
             nicotinic cholinergic receptors, or serotonin 5HT(2)
             receptors. This study shows that neonatal PTN exposure
             evokes long-term changes in behavior, but the effects are
             less severe, and in some incidences opposite in nature, to
             those seen earlier for CPF or DZN, findings consistent with
             our neurochemical studies showing different patterns of
             effects and less neurotoxic damage with PTN. Our results
             reinforce the conclusion that low dose exposure to different
             OPs can have quite different neurotoxic effects, obviously
             unconnected to their shared property as cholinesterase
             inhibitors.},
   Doi = {10.1016/j.brainresbull.2008.08.019},
   Key = {fds274266}
}

@article{fds274263,
   Author = {Levin, ED and Slade, S and Johnson, M and Petro, A and Horton, K and Williams, P and Rezvani, AH and Rose, JE},
   Title = {Ketanserin, a 5-HT2 receptor antagonist, decreases nicotine
             self-administration in rats.},
   Journal = {Eur J Pharmacol},
   Volume = {600},
   Number = {1-3},
   Pages = {93-97},
   Year = {2008},
   Month = {December},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/18950618},
   Abstract = {Nicotine intake constitutes a principal mechanism for
             tobacco addiction. In addition to primary effects on
             nicotinic acetylcholine receptors, nicotine has cascading
             effects, which may also underlie its neurobehavioral
             actions. Nicotine induces serotonin (5-HT) release, which
             has not classically been thought to be involved in tobacco
             addiction as dopamine has. However, addiction can be
             characterized more as a disorder of compulsion than a
             disorder of enjoyment. 5-HT mechanisms play key roles in
             compulsive disorders. Nicotine-induced 5-HT release may be a
             key to tobacco addiction. Ketanserin, a 5-HT2a and 5-HT2c
             receptor antagonist, significantly attenuates nicotine
             effects on attention and memory. These studies were
             conducted to determine if ketanserin would reduce nicotine
             self-administration in rats. Male Sprague-Dawley rats (N=12)
             were given initial food pellet training and then 10 sessions
             of nicotine self-administration training (0.03
             mg/kg/infusion, i.v.). Then the rats were administered
             ketanserin (1 or 2 mg/kg, s.c.) or the saline vehicle.
             Ketanserin (2 mg/kg) significantly decreased nicotine
             self-administration. This did not seem to be due to sedative
             or amnestic effects of ketanserin. In a second study, the
             effects of repeated administration of 2 mg/kg ketanserin
             (N=11) vs. saline injections (N=10) were examined. In the
             initial phase, the acute effectiveness of ketanserin in
             significantly reducing nicotine self-administration was
             replicated. The effect became attenuated during the
             following several sessions, but the significant effect
             became re-established during the final phases of this
             two-week study. 5-HT mechanisms play critical roles in the
             maintenance of nicotine self-administration. Better
             understanding of those roles may help lead to new 5-HT-based
             treatments for tobacco addiction.},
   Doi = {10.1016/j.ejphar.2008.10.016},
   Key = {fds274263}
}

@article{fds274249,
   Author = {Lassiter, TL and Ryde, IT and Mackillop, EA and Brown, KK and Levin, ED and Seidler, FJ and Slotkin, TA},
   Title = {Exposure of neonatal rats to parathion elicits sex-selective
             reprogramming of metabolism and alters the response to a
             high-fat diet in adulthood.},
   Journal = {Environmental Health Perspectives},
   Volume = {116},
   Number = {11},
   Pages = {1456-1462},
   Year = {2008},
   Month = {November},
   ISSN = {0091-6765},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/19057696},
   Abstract = {BACKGROUND: Developmental exposures to organophosphate
             pesticides are virtually ubiquitous. These agents are
             neurotoxicants, but recent evidence also points to lasting
             effects on metabolism. OBJECTIVES: We administered parathion
             to neonatal rats. In adulthood, we assessed the impact on
             weight gain, food consumption, and glucose and lipid
             homeostasis, as well as the interaction with the effects of
             a high-fat diet. METHODS: Neonatal rats were given parathion
             on postnatal days 1-4 using doses (0.1 or 0.2 mg/kg/day)
             that straddle the threshold for barely detectable
             cholinesterase inhibition and the first signs of systemic
             toxicity. In adulthood, animals were either maintained on
             standard lab chow or switched to a high-fat diet for 7
             weeks. RESULTS: In male rats on a normal diet, the low-dose
             parathion exposure caused increased weight gain but also
             evoked signs of a prediabetic state, with elevated fasting
             serum glucose and impaired fat metabolism. The higher dose
             of parathion reversed the weight gain and caused further
             metabolic defects. Females showed greater sensitivity to
             metabolic disruption, with weight loss at either parathion
             dose, and greater imbalances in glucose and lipid
             metabolism. At 0.1 mg/kg/day parathion, females showed
             enhanced weight gain on the high-fat diet; This effect was
             reversed in the 0.2-mg/kg/day parathion group, and was
             accompanied by even greater deficits in glucose and fat
             metabolism. CONCLUSIONS: Neonatal low-dose parathion
             exposure disrupts glucose and fat homeostasis in a
             persistent and sex-selective manner. Early-life toxicant
             exposure to organophosphates or other environmental
             chemicals may play a role in the increased incidence of
             obesity and diabetes.},
   Doi = {10.1289/ehp.11673},
   Key = {fds274249}
}

@article{fds274264,
   Author = {Bencan, Z and Levin, ED},
   Title = {The role of alpha7 and alpha4beta2 nicotinic receptors in
             the nicotine-induced anxiolytic effect in
             zebrafish.},
   Journal = {Physiology & Behavior},
   Volume = {95},
   Number = {3},
   Pages = {408-412},
   Year = {2008},
   Month = {October},
   ISSN = {0031-9384},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/18671990},
   Abstract = {Zebrafish (Danio rerio) have been widely used to study the
             molecular mechanisms of development including
             neurodevelopment. More recently, they have begun to be used
             to study neuropharmacology and neurotoxicology. Critical for
             this line of research are methods to study behavioral
             function in zebrafish. Previous studies have compared
             zebrafish with mammalian models to determine similarities
             and differences in locomotor behavior, learning and memory.
             Relatively little research has been conducted on stress
             response and anxiety behavior as well as the pharmacologic
             response in zebrafish. We have developed a test for
             zebrafish to assess stress response and anxiety: the novel
             tank diving test. In this short test normally zebrafish dive
             to the bottom of a novel tank and then gradually over the
             5-min test begin exploring higher levels of the tank.
             Nicotine, which has anxiolytic effects in rodents and humans
             was found to diminish this novel tank diving response in
             zebrafish. The current study examined the nicotinic receptor
             subtype selectivity involved in the actions of nicotine. Two
             nicotinic receptor subtype selective antagonists were used:
             MLA (an alpha7 antagonist) and DHbetaE (an alpha4beta2
             antagonist). We replicated our previous finding of the
             anxiolytic effect of nicotine with significantly less bottom
             dwelling by the fish after nicotine treatment. This
             nicotine-induced anxiolytic effect was reversed by both MLA
             and DHbetaE, indicating that both nicotinic alpha7 and
             alpha4beta2 receptors are involved in the nicotinic effect
             on anxiety in zebrafish.},
   Doi = {10.1016/j.physbeh.2008.07.009},
   Key = {fds274264}
}

@article{fds274248,
   Author = {Slotkin, TA and Bodwell, BE and Ryde, IT and Levin, ED and Seidler,
             FJ},
   Title = {Exposure of neonatal rats to parathion elicits sex-selective
             impairment of acetylcholine systems in brain regions during
             adolescence and adulthood.},
   Journal = {Environmental Health Perspectives},
   Volume = {116},
   Number = {10},
   Pages = {1308-1314},
   Year = {2008},
   Month = {October},
   ISSN = {0091-6765},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/18941570},
   Abstract = {Organophosphates elicit developmental neurotoxicity through
             multiple mechanisms other than their shared property as
             cholinesterase inhibitors. Accordingly, these agents may
             differ in their effects on specific brain circuits.We gave
             parathion to neonatal rats [postnatal days (PNDs) 1-4], at
             daily doses of 0.1 or 0.2 mg/kg, spanning the threshold for
             barely detectable cholinesterase inhibition and systemic
             effects.We assessed neurochemical indices related to the
             function of acetylcholine (ACh) synapses (choline
             acetyltransferase, presynaptic high-affinity choline
             transporter, nicotinic cholinergic receptors) in brain
             regions comprising all the major ACh projections, with
             determinations carried out from adolescence to adulthood
             (PNDs 30, 60, and 100).Parathion exposure elicited lasting
             alterations in ACh markers in the frontal/parietal cortex,
             temporal/occipital cortex, midbrain, hippocampus, and
             striatum. In cerebrocortical areas, midbrain, and
             hippocampus, effects in males were generally greater than in
             females, whereas in the striatum, females were targeted
             preferentially. Superimposed on this general pattern, the
             cerebrocortical effects showed a nonmonotonic dose-response
             relationship, with regression of the defects at the higher
             parathion dose; this relationship has been seen also after
             comparable treatments with chlorpyrifos and diazinon and
             likely represents the involvement of cholinesterase-related
             actions that mask or offset the effects of lower
             doses.Neonatal exposure to parathion, at doses straddling
             the threshold for cholinesterase inhibition, compromises
             indices of ACh synaptic function in adolescence and
             adulthood. Differences between the effects of parathion
             compared with chlorpyrifos or diazinon and the non-monotonic
             dose-effect relationships reinforce the conclusion that
             various organophosphates diverge in their effects on
             neurodevelopment, unrelated to their anticholinesterase
             actions.},
   Doi = {10.1289/ehp.11451},
   Key = {fds274248}
}

@article{fds274262,
   Author = {Timofeeva, OA and Levin, ED},
   Title = {Idazoxan blocks the nicotine-induced reversal of the memory
             impairment caused by the NMDA glutamate receptor antagonist
             dizocilpine.},
   Journal = {Pharmacology, Biochemistry, and Behavior},
   Volume = {90},
   Number = {3},
   Pages = {372-381},
   Year = {2008},
   Month = {September},
   ISSN = {0091-3057},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/18456310},
   Abstract = {RATIONALE: Alpha2-adrenoreceptor (alpha(2)-AR) antagonists
             have been shown to improve, while alpha(2)-AR agonists
             impair cognitive function in subjects with functioning NMDA
             receptors (NMDAR). In subjects with inhibited NMDAR (a model
             of schizophrenia) alpha(2)-AR agonists attenuate the
             cognitive impairments. The effect with alpha(2)-AR
             antagonists remains unclear. OBJECTIVES: We investigated the
             effects of the alpha(2)-AR antagonist idazoxan on memory
             function in rats treated/not treated with NMDAR antagonist
             dizocilpine or a combination of dizocilpine and nicotine to
             clarify noradrenergic/cholinergic regulation of memory
             function. METHODS: Female Sprague-Dawley rats (n=12) were
             trained for food reward on the radial maze. Working and
             reference memory errors and response latency were assessed
             after injections of idazoxan (0.5, 1.0 mg/kg), dizocilpine
             (0.05 mg/kg), nicotine (0.2, 0.4 mg/kg) or vehicle, alone or
             in combination. RESULTS: Dizocilpine potently impaired
             memory. Nicotine (0.4 mg/kg) reversed this impairment.
             Idazoxan at the doses tested did not affect performance when
             given alone or with dizocilpine, but it did block the
             nicotine reversal of the dizocilpine-induced memory
             impairment. Three rats after 10-12 drug treatments developed
             limbic seizures. Our findings suggest that combination of
             drugs which block alpha(2)-AR with nicotinic agonists in
             schizophrenia may prevent therapeutic effect of nicotinic
             agonists and increase risk for convulsive activity with
             repeated administration.},
   Doi = {10.1016/j.pbb.2008.03.011},
   Key = {fds274262}
}

@article{fds274260,
   Author = {Crofton, KM and Foss, JA and Hass, U and Jensen, KF and Levin, ED and Parker, SP},
   Title = {Undertaking positive control studies as part of
             developmental neurotoxicity testing: a report from the ILSI
             Research Foundation/Risk Science Institute expert working
             group on neurodevelopmental endpoints.},
   Journal = {Neurotoxicology and Teratology},
   Volume = {30},
   Number = {4},
   Pages = {266-287},
   Year = {2008},
   Month = {July},
   ISSN = {0892-0362},
   url = {http://dx.doi.org/10.1016/j.ntt.2007.06.002},
   Abstract = {Developmental neurotoxicity testing involves functional and
             neurohistological assessments in offspring during and
             following maternal and/or neonatal exposure. Data from
             positive control studies are an integral component in
             developmental neurotoxicity risk assessments. Positive
             control data are crucial for evaluating a laboratory's
             capability to detect chemical-induced changes in measured
             endpoints. Positive control data are also valuable in a
             weight-of-evidence approach to help determine the biological
             significance of results and provide confidence in negative
             results from developmental neurotoxicity (DNT) studies. This
             review is a practical guide for the selection and use of
             positive control agents in developmental neurotoxicology.
             The advantages and disadvantages of various positive control
             agents are discussed for the endpoints in developmental
             neurotoxicity studies. Design issues specific to positive
             control studies in developmental neurotoxicity are
             considered and recommendations on how to interpret and
             report positive control data are made. Positive control
             studies should be conducted as an integral component of the
             incorporation and use of developmental neurotoxicity testing
             methods in laboratories that generate data used in risk
             decisions.},
   Doi = {10.1016/j.ntt.2007.06.002},
   Key = {fds274260}
}

@article{fds274261,
   Author = {Rezvani, AH and Eddins, D and Slade, S and Hampton, DS and Christopher,
             NC and Petro, A and Horton, K and Johnson, M and Levin,
             ED},
   Title = {Neonatal 6-hydroxydopamine lesions of the frontal cortex in
             rats: persisting effects on locomotor activity, learning and
             nicotine self-administration.},
   Journal = {Neuroscience},
   Volume = {154},
   Number = {3},
   Pages = {885-897},
   Year = {2008},
   Month = {June},
   ISSN = {0306-4522},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/18511204},
   Abstract = {Dopaminergic innervation of the frontal cortex in adults is
             important for a variety of cognitive functions and
             behavioral control. However, the role of frontal cortical
             dopaminergic innervation for neurobehavioral development has
             received little attention. In the current study, rats were
             given dopaminergic lesions in the frontal cortex with local
             micro-infusions of 6-hydroxydopamine (6-OHDA) at 1 week of
             age. The long-term behavioral effects of neonatal frontal
             cortical 6-OHDA lesions were assessed in a series of tests
             of locomotor activity, spatial learning and memory, and i.v.
             nicotine self-administration. In addition, neurochemical
             indices were assessed with tissue homogenization and HPLC in
             the frontal cortex, striatum, and nucleus accumbens of
             neonatal and adult rats after neonatal 6-OHDA lesions. In
             neonatal rats, frontal 6-OHDA lesions as intended caused a
             significant reduction in frontal cortical dopamine without
             effects on frontal cortical 5-HT and norepinephrine. The
             frontal cortical dopamine depletion increased 5-HT and
             norepinephrine levels in the nucleus accumbens. Locomotor
             activity assessment during adulthood in the figure-8 maze
             showed that lesioned male rats were hyperactive relative to
             sham-lesioned males. Locomotor activity of female rats was
             not significantly affected by the neonatal frontal 6-OHDA
             lesion. Learning and memory in the radial-arm maze was also
             affected by neonatal frontal 6-OHDA lesions. There was a
             general trend toward impaired performance in early maze
             acquisition and a paradoxical improvement at the end of
             cognitive testing. Nicotine self-administration showed
             significant lesion x sex interactions. The sex difference in
             nicotine self-administration with females self-administering
             significantly more nicotine than males was reversed by
             neonatal 6-OHDA frontal cortical lesions. Neurochemical
             studies in adult rats showed that frontal cortical dopamine
             and DOPAC levels significantly correlated with nicotine
             self-administration in the 6-OHDA-lesioned animals but not
             in the controls. Frontal cortical 5-HT and 5HIAA showed
             inverse correlations with nicotine self-administration in
             the 6-OHDA-lesioned animals but not in the controls. These
             results show that interfering with normal dopamine
             innervation of the frontal cortex during early postnatal
             development has persisting behavioral effects, which are
             sex-specific.},
   Doi = {10.1016/j.neuroscience.2008.04.020},
   Key = {fds274261}
}

@article{fds274257,
   Author = {Morey, JS and Ryan, JC and Bottein Dechraoui and M-Y and Rezvani, AH and Levin, ED and Gordon, CJ and Ramsdell, JS and Van Dolah,
             FM},
   Title = {Liver genomic responses to ciguatoxin: evidence for
             activation of phase I and phase II detoxification pathways
             following an acute hypothermic response in
             mice.},
   Journal = {Toxicological Sciences},
   Volume = {103},
   Number = {2},
   Pages = {298-310},
   Year = {2008},
   Month = {June},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/18353800},
   Abstract = {Ciguatoxins (CTX) are polyether neurotoxins that target
             voltage-gated sodium channels and are responsible for
             ciguatera, the most common fish-borne food poisoning in
             humans. This study characterizes the global transcriptional
             response of mouse liver to a symptomatic dose (0.26 ng/g) of
             the highly potent Pacific ciguatoxin-1 (P-CTX-1). At 1 h
             post-exposure 2.4% of features on a 44K whole genome array
             were differentially expressed (p < or = 0.0001), increasing
             to 5.2% at 4 h and decreasing to 1.4% by 24 h post-CTX
             exposure. Data were filtered (/fold change/ > or = 1.5 and p
             < or = 0.0001 in at least one time point) and a trend set of
             1550 genes were used for further analysis. Early gene
             expression was likely influenced prominently by an acute 4
             degrees C decline in core body temperature by 1 h, which
             resolved by 8 h following exposure. An initial
             downregulation of 32 different solute carriers, many
             involved in sodium transport, was observed. Differential
             gene expression in pathways involving eicosanoid
             biosynthesis and cholesterol homeostasis was also noted.
             Cytochrome P450s (Cyps) were of particular interest due to
             their role in xenobiotic metabolism. Twenty-seven genes,
             mostly members of Cyp2 and Cyp4 families, showed significant
             changes in expression. Many Cyps underwent an initial
             downregulation at 1 h but were quickly and strongly
             upregulated at 4 and 24 h post-exposure. In addition to
             Cyps, increases in several glutathione S-transferases were
             observed, an indication that both phase I and phase II
             metabolic reactions are involved in the hepatic response to
             CTX in mice.},
   Doi = {10.1093/toxsci/kfn055},
   Key = {fds274257}
}

@article{fds274259,
   Author = {Rezvani, AH and Tizabi, Y and Getachew, B and Hauser, SR and Caldwell,
             DP and Hunter, C and Levin, ED},
   Title = {Chronic nicotine and dizocilpine effects on nicotinic and
             NMDA glutamatergic receptor regulation: interactions with
             clozapine actions and attentional performance in
             rats.},
   Journal = {Progress in Neuro Psychopharmacology & Biological
             Psychiatry},
   Volume = {32},
   Number = {4},
   Pages = {1030-1040},
   Year = {2008},
   Month = {May},
   ISSN = {0278-5846},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/18343006},
   Abstract = {Blockade of NMDA glutamate receptors with dizocilpine
             (MK-801) has been shown to cause substantial cognitive
             deficits and has been used to model symptoms of
             schizophrenia. Nicotine or nicotinic agonists, in contrast,
             may enhance cognitive or attentional functions and be of
             therapeutic potential in schizophrenia. Nicotinic-glutamatergic
             interactions, therefore, may have important implications in
             cognitive functions and antipsychotic treatments. Clozapine,
             a widely used antipsychotic drug, has been shown in some
             studies to be effective in ameliorating the cognitive
             deficits associated with schizophrenia. However, there is
             some evidence to suggest that clozapine similar to
             haloperidol may impair sustained attention in rats. In this
             study, we sought to determine whether chronic nicotine or
             dizocilpine may modify the effects of acute clozapine on
             attentional parameters and whether the behavioral effects
             would correlate with nicotinic or NMDA receptor densities in
             discrete brain regions. Adult female rats trained on an
             operant visual signal detection task were given 4 weeks of
             nicotine (5 mg/kg/day), dizocilpine (0.15 mg/kg/day), the
             same doses of both nicotine and dizocilpine as a mixture, or
             saline by osmotic minipump. While on chronic treatment, rats
             received acute injections of various doses of clozapine (0,
             0.625, 1.25, 2.5 mg/kg, sc) 10 min prior to tests on
             attentional tasks. The pumps were removed on day 28 and 24 h
             later the animals were sacrificed for measurements of
             receptor densities in specific brain regions. The percent
             correct hit as a measure of sustained attention was
             significantly impaired by clozapine in a dose-related
             manner. Neither chronic nicotine nor dizocilpine affected
             this measure on their own or modified the effects of
             clozapine. Both nicotine and dizocilpine affected the
             receptor bindings in a region specific manner and their
             combination further modified the effects of each other in
             selective regions. Attentional performance was inversely
             correlated with alpha-bungarotoxin binding in the frontal
             cortex only. In conclusion, the data suggest attentional
             impairments with clozapine alone and no modification of this
             effect with nicotine or dizocilpine. Moreover, cortical low
             affinity nicotinic receptors may have a role in attentional
             functions.},
   Doi = {10.1016/j.pnpbp.2008.01.018},
   Key = {fds274259}
}

@article{fds274258,
   Author = {West, AK and Hidalgo, J and Eddins, D and Levin, ED and Aschner,
             M},
   Title = {Metallothionein in the central nervous system: Roles in
             protection, regeneration and cognition.},
   Journal = {Neurotoxicology},
   Volume = {29},
   Number = {3},
   Pages = {489-503},
   Year = {2008},
   Month = {May},
   ISSN = {0161-813X},
   url = {http://dx.doi.org/10.1016/j.neuro.2007.12.006},
   Abstract = {Metallothionein (MT) is an enigmatic protein, and its
             physiological role remains a matter of intense study and
             debate 50 years after its discovery. This is particularly
             true of its function in the central nervous system (CNS),
             where the challenge remains to link its known biochemical
             properties of metal binding and free radical scavenging to
             the intricate workings of brain. In this compilation of four
             reports, first delivered at the 11th International
             Neurotoxicology Association (INA-11) Meeting, June 2007, the
             authors present the work of their laboratories, each of
             which gives an important insight into the actions of MT in
             the brain. What emerges is that MT has the potential to
             contribute to a variety of processes, including
             neuroprotection, regeneration, and even cognitive functions.
             In this article, the properties and CNS expression of MT are
             briefly reviewed before Dr Hidalgo describes his pioneering
             work using transgenic models of MT expression to demonstrate
             how this protein plays a major role in the defence of the
             CNS against neurodegenerative disorders and other CNS
             injuries. His group's work leads to two further questions,
             what are the mechanisms at the cellular level by which MT
             acts, and does this protein influence higher order issues of
             architecture and cognition? These topics are addressed in
             the second and third sections of this review by Dr West, and
             Dr Levin and Dr Eddins, respectively. Finally, Dr Aschner
             examines the ability of MT to protect against a specific
             toxicant, methylmercury, in the CNS.},
   Doi = {10.1016/j.neuro.2007.12.006},
   Key = {fds274258}
}

@article{fds274255,
   Author = {Bottein Dechraoui and M-Y and Rezvani, AH and Gordon, CJ and Levin, ED and Ramsdell, JS},
   Title = {Repeat exposure to ciguatoxin leads to enhanced and
             sustained thermoregulatory, pain threshold and motor
             activity responses in mice: relationship to blood ciguatoxin
             concentrations.},
   Journal = {Toxicology},
   Volume = {246},
   Number = {1},
   Pages = {55-62},
   Year = {2008},
   Month = {April},
   ISSN = {0300-483X},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/18280027},
   Abstract = {Ciguatera is a common illness in tropical and subtropical
             regions that manifests in complex and long-lived symptoms
             which are more severe in subsequent exposures. This study
             measures central and peripheral neurologic signs, in
             parallel with blood toxin levels, in mice exposed once or
             twice (at 3 days interval) to a sublethal dose of ciguatoxin
             P-CTX-1 (0.26ng/g via i.p.). Mice were implanted with
             radiotransmitters to monitor motor activity and core
             temperature. A single exposure to ciguatoxin elicited an
             immediate and transient decrease in motor activity and
             temperature, and subsequent long-lasting thermoregulatory
             dysfunction resulting in stabilized body temperature around
             36.0 degrees C with no observable circadian rhythm. The
             hypothermic response and the reduced activity were enhanced
             with a second exposure with 30% of the mice dying within 7h.
             Measurement of the peripheral nervous system by the tail
             flick assay revealed increased latency with a single
             ciguatoxin exposure, and a greater effect following the
             second exposure. Toxin was measurable in blood up to 3 days
             following the first exposure; at the 1h time point the
             concentrations were significantly elevated after a second
             exposure. These findings indicate an early response to
             ciguatoxin manifest in a central response to lower body
             temperature and reduce motor activity and a more persistent
             effect on the peripheral system leading to spinal heat
             antinociception and delayed fever-like response. The greater
             neurological response to a second ciguatoxin exposure was
             associated with elevated concentrations of ciguatoxin in the
             blood solely over the first hour of exposure. In conclusion,
             a single exposure to toxin exerts a significant neurological
             response which may be enhanced with subsequent
             exposure.},
   Doi = {10.1016/j.tox.2007.12.013},
   Key = {fds274255}
}

@article{fds274253,
   Author = {Slotkin, TA and Ryde, IT and Levin, ED and Seidler,
             FJ},
   Title = {Developmental neurotoxicity of low dose diazinon exposure of
             neonatal rats: effects on serotonin systems in adolescence
             and adulthood.},
   Journal = {Brain Research Bulletin},
   Volume = {75},
   Number = {5},
   Pages = {640-647},
   Year = {2008},
   Month = {March},
   ISSN = {0361-9230},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/18355640},
   Abstract = {The developmental neurotoxicity of organophosphate
             pesticides targets serotonin (5HT) systems, which are
             involved in emotional and appetitive behaviors. We exposed
             neonatal rats to daily doses of diazinon on postnatal days
             1-4, using doses (0.5 or 2mg/kg) spanning the threshold for
             barely-detectable cholinesterase inhibition. We then
             evaluated the effects on 5HT(1A) and 5HT(2) receptors, and
             on the 5HT transporter in cerebral cortical regions and the
             brainstem in adolescence through adulthood. Diazinon evoked
             a lasting deficit in 5HT(1A) receptors in males only,
             whereas it caused a small but significant increase in 5HT
             transporters in females; neither effect showed a significant
             regional selectivity. This pattern differed substantially
             from that seen in earlier work with another organophosphate,
             chlorpyrifos, which at pharmacodynamically similar doses
             spanning the threshold for cholinesterase inhibition, evoked
             a much more substantial, global upregulation of 5HT receptor
             expression; with chlorpyrifos, effects on receptors were
             seen in females, albeit to a lesser extent than in males,
             and were also regionally distinct. The effects of diazinon
             were nonmonotonic, showing larger alterations at the lower
             dose, likely reflecting positive trophic effects of
             cholinergic stimulation once the threshold for
             cholinesterase inhibition is exceeded. Our results reinforce
             the idea that different organophosphates have fundamentally
             distinct effects on the developmental trajectories of
             specific neurotransmitter systems, unrelated to their shared
             action as cholinesterase inhibitors. The effects on 5HT
             circuits expand the scope of behavioral endpoints that need
             to be considered in evaluating the developmental
             neurotoxicity of organophosphates.},
   Doi = {10.1016/j.brainresbull.2007.10.008},
   Key = {fds274253}
}

@article{fds274252,
   Author = {Eddins, D and Petro, A and Pollard, N and Freedman, JH and Levin,
             ED},
   Title = {Mercury-induced cognitive impairment in metallothionein-1/2
             null mice.},
   Journal = {Neurotoxicology and Teratology},
   Volume = {30},
   Number = {2},
   Pages = {88-95},
   Year = {2008},
   Month = {March},
   ISSN = {0892-0362},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/18226494},
   Abstract = {Metallothioneins are central for the metabolism and
             detoxification of transition metals. Exposure to mercury
             during early neurodevelopment is associated with
             neurocognitive impairment. Given the importance of
             metallothioneins in mercury detoxification, metallothioneins
             may be a protective factor against mercury-induced
             neurocognitive impairment. Deletion of the murine
             metallothionein-1 and metallothionein-2 genes causes choice
             accuracy impairments in the 8-arm radial maze. We
             hypothesize that deletions of metallothioneins genes will
             make metallothionein-null mice more vulnerable to
             mercury-induced cognitive impairment. We tested this
             hypothesis by exposing MT1/MT2-null and wild-type mice to
             developmental mercury (HgCl(2)) and evaluated the resultant
             effects on cognitive performance on the 8-arm radial maze.
             During the early phase of learning metallothionein-null mice
             were more susceptible to mercury-induced impairment compared
             to wildtype mice. Neurochemical analysis of the frontal
             cortex revealed that serotonin levels were higher in
             metallothionein-null mice compared to wild-type mice. This
             effect was independent of mercury exposure. However,
             dopamine levels in mercury-exposed metallothionein-null mice
             were lower compared to mercury-exposed wild-type mice. This
             work shows that deleting metallothioneins increase the
             vulnerability to developmental mercury-induced
             neurocognitive impairment. Metallothionein effects on
             monoamine transmitters may be related to this cognitive
             effect.},
   Doi = {10.1016/j.ntt.2007.12.005},
   Key = {fds274252}
}

@article{fds274254,
   Author = {Slotkin, TA and Bodwell, BE and Levin, ED and Seidler,
             FJ},
   Title = {Neonatal exposure to low doses of diazinon: long-term
             effects on neural cell development and acetylcholine
             systems.},
   Journal = {Environmental Health Perspectives},
   Volume = {116},
   Number = {3},
   Pages = {340-348},
   Year = {2008},
   Month = {March},
   ISSN = {0091-6765},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/18335101},
   Abstract = {BACKGROUND: The developmental neurotoxicity of
             organophosphate pesticides involves mechanisms other than
             their shared property of cholinesterase inhibition.
             OBJECTIVES: We gave diazinon (DZN) to newborn rats on
             postnatal days 1-4, using doses (0.5 or 2 mg/kg) spanning
             the threshold for barely detectable cholinesterase
             inhibition. METHODS: We then evaluated the lasting effects
             on indices of neural cell number and size, and on functional
             markers of acetylcholine (ACh) synapses (choline
             acetyltransferase, presynaptic high-affinity choline
             transporter, nicotinic cholinergic receptors) in a variety
             of brain regions. RESULTS: DZN exposure produced a
             significant overall increase in cell-packing density in
             adolescence and adulthood, suggestive of neuronal loss and
             reactive gliosis; however, some regions (temporal/occipital
             cortex, striatum) showed evidence of net cell loss,
             reflecting a greater sensitivity to neurotoxic effects of
             DZN. Deficits were seen in ACh markers in cerebrocortical
             areas and the hippocampus, regions enriched in ACh
             projections. In contrast, there were no significant effects
             in the midbrain, the major locus for ACh cell bodies. The
             striatum showed a unique pattern, with robust initial
             elevations in the ACh markers that regressed in adulthood to
             normal or subnormal values. CONCLUSIONS: These results
             indicate that developmental exposures to apparently nontoxic
             doses of DZN compromise neural cell development and alter
             ACh synaptic function in adolescence and adulthood. The
             patterns seen here differ substantially from those seen in
             earlier work with chlorpyrifos, reinforcing the concept that
             the various organophosphates have fundamentally different
             effects on the developmental trajectories of specific
             neurotransmitter systems, unrelated to their shared action
             as cholinesterase inhibitors.},
   Doi = {10.1289/ehp.11005},
   Key = {fds274254}
}

@article{fds274251,
   Author = {Rezvani, AH and Kholdebarin, E and Dawson, E and Levin,
             ED},
   Title = {Nicotine and clozapine effects on attentional performance
             impaired by the NMDA antagonist dizocilpine in female
             rats.},
   Journal = {The International Journal of Neuropsychopharmacology},
   Volume = {11},
   Number = {1},
   Pages = {63-70},
   Year = {2008},
   Month = {February},
   ISSN = {1461-1457},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/17295931},
   Abstract = {Cognitive impairment is very prevalent in schizophrenia and
             is currently undertreated in most patients. Attentional
             deficit is one of the hallmark symptoms of schizophrenia.
             Antipsychotic drugs, which can be quite effective in
             combating hallucinations are often ineffective in reducing
             cognitive impairment and can potentiate cognitive
             impairment. Previously, we found that the antipsychotic drug
             clozapine impaired, while nicotine improved, the accuracy of
             rats performing a visual signal detection attentional task
             in normal rats. For the current study, in a model of
             cognitive impairment of schizophrenia with the NMDA
             antagonist dizocilpine (0.05 mg/kg), we examined the effects
             of clozapine and nicotine on significantly impaired
             attentional hit accuracy. This dizocilpine-induced
             impairment was significantly (p<0.05) reversed by either
             clozapine (1.25 mg/kg) or nicotine (0.025 mg/kg).
             Interestingly, when clozapine and nicotine were given
             together, they blocked each other's beneficial effects. When
             the effective doses of 1.25 mg/kg clozapine and 0.025 mg/kg
             nicotine were given together the combination no longer
             significantly reversed the dizocilpine-induced hit-accuracy
             impairment. Given that the great majority of people with
             schizophrenia smoke, the potential beneficial effects of
             clozapine on attentional function may be largely blocked by
             self-administered nicotine. In addition, there are promising
             results concerning the development of nicotinic treatments
             to reverse cognitive deficits including attentional
             impairment. This is supported in the current study by the
             reversal of the dizocilpine-induced attentional impairment
             by nicotine. However, in schizophrenia the efficacy of
             nicotinic treatments may be limited by co-treatment with
             antipsychotic drugs like clozapine. It will be important to
             determine which of the complex effects of clozapine and
             nicotine are key in reversing attentional impairment and how
             they block each other's effects for the development of
             therapy to combat the attentional impairment of
             schizophrenia.},
   Doi = {10.1017/S1461145706007528},
   Key = {fds274251}
}

@article{fds274250,
   Author = {Roegge, CS and Timofeeva, OA and Seidler, FJ and Slotkin, TA and Levin,
             ED},
   Title = {Developmental diazinon neurotoxicity in rats: later effects
             on emotional response.},
   Journal = {Brain Research Bulletin},
   Volume = {75},
   Number = {1},
   Pages = {166-172},
   Year = {2008},
   Month = {January},
   ISSN = {0361-9230},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/18158111},
   Abstract = {Developmental exposure to the organophosphorus pesticides
             chlorpyrifos and diazinon (DZN) alters serotonergic synaptic
             function at doses below the threshold for cholinesterase
             inhibition, however there are some indications that the two
             agents may differ in several important attributes.
             Previously, we found that low-dose chlorpyrifos exposure in
             neonatal rats causes lasting changes in emotional response
             and in the current study we did a comparable evaluation for
             DZN. Male and female Sprague-Dawley rat pups (N=10-12 of
             each sex per treatment group) were given 0, 0.5 or 2 mg/(kg
             day) of DZN s.c. daily on postnatal days (PND) 1-4. These
             doses bracket the threshold for barely-detectable
             cholinesterase inhibition. Starting on PND 52, these rats
             began a battery of tests to assess emotional reactivity. In
             the elevated plus maze, there was a slight decrease in the
             time spent in the open arms for DZN-exposed males, while
             DZN-exposed females were not different from control females.
             In the novelty-suppressed feeding test, DZN-exposed males
             had significantly shorter latencies to begin eating than did
             control males, reducing the values to those normally seen in
             females. DZN-exposed rats of either sex showed reduced
             preference for chocolate milk in the anhedonia test that
             compared the consumption of chocolate milk to water. These
             findings show that neonatal exposures to DZN at a dose range
             below the threshold for cholinesterase inhibition
             nevertheless evokes specific, later alterations in emotional
             behaviors, particularly in males. The effects show not only
             some similarities to those of chlorpyrifos but also some
             differences, in keeping with neurochemical findings
             comparing the two agents.},
   Doi = {10.1016/j.brainresbull.2007.08.008},
   Key = {fds274250}
}

@article{fds274247,
   Author = {Timofeeva, OA and Roegge, CS and Seidler, FJ and Slotkin, TA and Levin,
             ED},
   Title = {Persistent cognitive alterations in rats after early
             postnatal exposure to low doses of the organophosphate
             pesticide, diazinon.},
   Journal = {Neurotoxicology and Teratology},
   Volume = {30},
   Number = {1},
   Pages = {38-45},
   Year = {2008},
   Month = {January},
   ISSN = {0892-0362},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/18096363},
   Abstract = {BACKGROUND: Developmental neurotoxicity of organophosphorous
             insecticides (OPs) involves multiple mechanisms in addition
             to cholinesterase inhibition. We have found persisting
             effects of developmental chlorpyrifos (CPF) and diazinon
             (DZN) on cholinergic and serotonergic neurotransmitter
             systems and gene expression as well as behavioral function.
             Both molecular/neurochemical and behavioral effects of
             developmental OP exposure have been seen at doses below
             those which cause appreciable cholinesterase inhibition.
             OBJECTIVES: We sought to determine if developmental DZN
             exposure at doses which do not produce significant
             acetylcholinesterase inhibition cause persisting cognitive
             deficits. METHODS: Rats were exposed to DZN on postnatal
             days 1-4 at doses (0.5 and 2 mg/kg/d) that span the
             threshold for cholinesterase inhibition. They were later
             examined with a cognitive battery tests similar to that used
             with CPF. RESULTS: In the T-maze DZN caused significant
             hyperactivity in the initial trials of the session, but not
             later. In a longer assessment of locomotor activity no
             DZN-induced changes were seen over a 1-hour session.
             Prepulse inhibition was reduced by DZN exposure selectively
             in males vs. females; DZN eliminated the sex difference
             present in controls. In the radial maze, the lower but not
             higher DZN dose significantly impaired spatial learning.
             This type of nonmonotonic dose-effect function has
             previously been seen with CPF as well. The lower dose DZN
             group also showed significantly greater sensitivity to the
             memory-impairing effects of scopolamine a muscarinic
             acetylcholine antagonist. CONCLUSIONS: Neonatal DZN exposure
             below the threshold for appreciable cholinesterase
             inhibition caused persisting neurocognitive deficits in
             adulthood. The addition of some inhibition of AChE with a
             higher dose reversed the cognitive impairment. This
             non-monotonic dose-effect function has also been seen with
             neurochemical effects. Some of the DZN effects on cognition
             resemble those seen earlier for CPF, some differ. Our data
             suggest that DZN and CPF affect transmitter systems
             supporting memory function, differently, implying
             participation of mechanisms other than their common
             inhibition of cholinesterase.},
   Doi = {10.1016/j.ntt.2007.10.002},
   Key = {fds274247}
}

@article{fds274244,
   Author = {Ryan, JC and Bottein Dechraoui and M-Y and Morey, JS and Rezvani, A and Levin, ED and Gordon, CJ and Ramsdell, JS and Van Dolah,
             FM},
   Title = {Transcriptional profiling of whole blood and serum protein
             analysis of mice exposed to the neurotoxin Pacific
             Ciguatoxin-1.},
   Journal = {Neurotoxicology},
   Volume = {28},
   Number = {6},
   Pages = {1099-1109},
   Year = {2007},
   Month = {November},
   ISSN = {0161-813X},
   url = {http://dx.doi.org/10.1016/j.neuro.2007.05.013},
   Abstract = {Ciguatoxins (CTX) are a suite of cyclic polyether toxins
             produced by the marine dinoflagellate Gambierdiscus sp., are
             potent activators of voltage-gated sodium channels and a
             leading cause of human poisoning from food fish. This report
             characterizes the genomic and proteomic response in whole
             blood of adult male mice exposed i.p. to 264 ng/kg of the
             Pacific congener of CTX (P-CTX-1) at 1, 4 and 24h. Whole
             genome microarray expression data were filtered by tightness
             of fit between replicates, fold change (1.8) and p-value
             (10(-5)), resulting in 183 annotated genes used for trending
             analysis, K-means clustering and ontology classification.
             Genes involved with cytokine signaling, proteasome complex
             and ribosomal function were dominant. qPCR performed on 19
             genes of interest had a correlation of 0.95 to array results
             by Pearson's correlation coefficient. Serum protein analysis
             showed small but significant changes in 6 of 60 proteins
             assayed: Ccl2, Ccl12, CD40, IL-10, leptin and M-CSF. In
             large part, the gene expression was consistent with a Th2
             immune response with interesting similarities to expression
             seen in asthmatic models.},
   Doi = {10.1016/j.neuro.2007.05.013},
   Key = {fds274244}
}

@article{fds274245,
   Author = {Levin, ED and Rezvani, AH},
   Title = {Nicotinic interactions with antipsychotic drugs, models of
             schizophrenia and impacts on cognitive function.},
   Journal = {Biochemical Pharmacology},
   Volume = {74},
   Number = {8},
   Pages = {1182-1191},
   Year = {2007},
   Month = {October},
   ISSN = {0006-2952},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/17714691},
   Abstract = {People with schizophrenia often have substantial cognitive
             impairments, which may be related to nicotinic receptor
             deficits, (alpha7 and alpha4beta2), documented in the brains
             of people with schizophrenia. The large majority of people
             with schizophrenia smoke cigarettes. Thus, nicotinic
             interactions with antipsychotic drugs are widespread.
             Complementary co-therapies of novel nicotinic ligands are
             being developed to add to antipsychotic therapy to treat the
             cognitive impairment of schizophrenia. Thus, it is critical
             to understand the interaction between nicotinic treatments
             and antipsychotic drugs. Nicotinic interactions with
             antipsychotic drugs, are complex since both nicotine and
             antipsychotics have complex actions. Nicotine stimulates and
             desensitizes nicotinic receptors of various subtypes and
             potentiates the release of different neurotransmitters.
             Antipsychotics also act on a verity of receptor systems. For
             example, clozapine acts as an antagonist at a variety of
             neurotransmitter receptors such as those for dopamine,
             serotonin, norepinepherine and histamine. In a series of
             studies, we have found that in normally functioning rats,
             moderate doses of clozapine impair working memory and that
             clozapine blocks nicotine-induced memory and attentional
             improvement. Clozapine and nicotine can attenuate each
             other's beneficial effects in reversing the memory
             impairment caused by the psychototmimetic drug dizocilpine.
             A key to the clozapine-induced attenuation of
             nicotine-induced cognitive improvement appears to be its
             5HT(2) antagonist properties. The selective 5HT(2)
             antagonist ketanserin has a similar action of blocking
             nicotine-induced memory and attentional improvements. It is
             important to consider the interactions between nicotinic and
             antipsychotic drugs to develop the most efficacious
             treatment for cognitive improvement in people with
             schizophrenia.},
   Doi = {10.1016/j.bcp.2007.07.019},
   Key = {fds274245}
}

@article{fds274246,
   Author = {Kholdebarin, E and Caldwell, DP and Blackwelder, WP and Kao, M and Christopher, NC and Levin, ED},
   Title = {Interaction of nicotinic and histamine H(3) systems in the
             radial-arm maze repeated acquisition task.},
   Journal = {European Journal of Pharmacology},
   Volume = {569},
   Number = {1-2},
   Pages = {64-69},
   Year = {2007},
   Month = {August},
   ISSN = {0014-2999},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/17544392},
   Abstract = {Nicotinic systems have been found in a variety of studies to
             play important roles in cognitive function. Nicotinic
             involvement in different aspects of cognitive function such
             as learning vs. memory may differ. We have found in rats
             that the spatial repeated acquisition task in the radial-arm
             maze is significantly improved by low doses of the nicotinic
             receptor antagonist mecamylamine, the atypical nicotinic
             receptor ligand lobeline, as well as the alpha7 nicotinic
             receptor agonist ARR-17779. Interestingly, nicotine in the
             same dose range that improves working memory in the
             win-shift radial maze task was not effective in improving
             repeated acquisition performance. Nicotinic systems interact
             with a variety of other neural systems. Differential
             involvement of these extended effects with learning vs.
             memory may help explain differential effects of nicotinic
             drugs with these cognitive functions. Histamine H(3)
             receptor antagonists have been shown by some studies to
             improve cognitive function, but others have not found this
             effect and some have found impairment. Nicotine stimulates
             the release of histamine. This effect may counter other
             cascading effects of nicotine in the performance of learning
             and memory tasks. A specific test of this hypothesis
             involves our study of nicotine (0.1-0.4 mg/kg) interactions
             with the histamine H(3) receptor antagonist thioperamide
             (2.5-10 mg/kg) on learning memory in the repeated
             acquisition test in the radial-arm maze. The highest dose of
             thioperamide tested caused a significant choice accuracy
             impairment, which was most evident during the later portions
             of the learning curve. The highest dose of nicotine did not
             change overall errors but did cause a significant impairment
             in learning over trials. The choice accuracy impairment
             induced by thioperamide was significantly attenuated by
             nicotine (0.4 mg/kg). The learning impairment caused by the
             highest dose of nicotine was significantly attenuated by
             thioperamide. Thioperamide also caused a slowing of
             response, an effect, which was attenuated by nicotine
             co-administration. The repeated acquisition test can help
             differentiate acute drug effects on learning. Nicotine and
             thioperamide effectively reversed each other's choice
             accuracy impairment even though each by itself impaired
             accuracy.},
   Doi = {10.1016/j.ejphar.2007.04.051},
   Key = {fds274246}
}

@article{fds274242,
   Author = {Levin, ED and Lawrence, SS and Petro, A and Horton, K and Rezvani, AH and Seidler, FJ and Slotkin, TA},
   Title = {Adolescent vs. adult-onset nicotine self-administration in
             male rats: duration of effect and differential nicotinic
             receptor correlates.},
   Journal = {Neurotoxicology and Teratology},
   Volume = {29},
   Number = {4},
   Pages = {458-465},
   Year = {2007},
   Month = {July},
   ISSN = {0892-0362},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/17433619},
   Abstract = {Adolescence is the life stage when tobacco addiction
             typically begins. Adolescent neurobehavioral development may
             be altered by nicotine self-administration in a way that
             persistently potentiates addiction. Previously, we showed
             that female adolescent rats self-administer more nicotine
             than do adults and that the increased nicotine intake then
             persists through the transition to adulthood [E.D. Levin, A.
             Rezvani, D. Montoya, J. Rose, H. Swartzwelder,
             Adolescent-onset nicotine self-administration modeled in
             female rats, Psychopharmacology 169 (2003) 141-149.]. In the
             current study, male Sprague-Dawley rats were given access to
             nicotine via the standard operant IV self-administration
             procedure (nicotine bitartrate dose of 0.03 mg/kg/infusion).
             One group of male rats started during adolescence the other
             group started in young adulthood. After the end of the
             four-week period of self-administration brain regions of the
             rats were assessed for alpha4beta2 nicotinic receptor
             binding. We found that male rats, like females, show higher
             nicotine self-administration when starting during
             adolescence as compared to starting in adulthood (p<0.001).
             Indeed, the effect in adolescent males was even greater than
             that in females, with more than triple the rate of nicotine
             self-administration vs. the adult-onset group during the
             first 2 weeks. The adolescent onset nicotine-self-administering
             rats also had significantly greater high affinity nicotinic
             receptor binding in the midbrain and the striatum, whereas
             hippocampal binding did not differ between the age groups.
             Striatal values significantly correlated with nicotine
             self-administration during the first 2 weeks in the
             adult-onset group but not the adolescent-onset rats,
             suggesting that the differences in self-administration may
             depend in part on underlying disparities in synaptic
             responses to nicotine. After the initial 2 weeks, nicotine
             self-administration in male rats declined toward adult-like
             levels, as the adolescent rats approached adulthood. This
             study showed that adolescent male rats self-administer
             significantly more nicotine than do male adult rats, but
             that adolescent-onset nicotine self-administration in male
             rats declines over weeks of continued use to approach
             adult-onset levels. In a previous study, we found that
             female rats also show greater nicotine self-administration
             with adolescent onset vs. adult onset, but that the females
             continued higher rates of self-administration into
             adulthood. Our results thus reinforce the concept that the
             adolescent brain is unusually receptive to the effects of
             nicotine in a manner that reinforces the potential for
             addiction.},
   Doi = {10.1016/j.ntt.2007.02.002},
   Key = {fds274242}
}

@article{fds274243,
   Author = {Roegge, CS and Perraut, C and Hao, X and Levin, ED},
   Title = {Histamine H1 receptor involvement in prepulse inhibition and
             memory function: relevance for the antipsychotic actions of
             clozapine.},
   Journal = {Pharmacology, Biochemistry, and Behavior},
   Volume = {86},
   Number = {4},
   Pages = {686-692},
   Year = {2007},
   Month = {April},
   ISSN = {0091-3057},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/17382376},
   Abstract = {Histamine H(1) blockade is one of the more prominent actions
             of the multi-receptor acting antipsychotic clozapine. It is
             currently not known how much this H(1) antagonism of
             clozapine contributes to the therapeutic or adverse side
             effects of clozapine. The current studies with
             Sprague-Dawley rats were conducted to determine the
             participation of histaminergic H(1) receptor subtype in
             sensorimotor plasticity and memory function affected by
             clozapine using tests of prepulse inhibition (PPI) and
             radial-arm maze choice accuracy. The PPI impairment caused
             by the glutamate antagonist dizocilpine (MK-801) was
             significantly attenuated by clozapine. In the current
             project, we found that the selective H(1) antagonist
             pyrilamine also reversed the dizocilpine-induced impairment
             in PPI of tactile startle with an auditory prepulse. In the
             radial-arm maze (RAM), pyrilamine, like clozapine, impaired
             working memory and caused a significant dose-related slowing
             of response. Pyrilamine, however, decreased the number of
             reference memory errors. We have previously shown that
             nicotine effectively attenuates the clozapine-induced
             working memory impairment, but in the current study,
             nicotine did not significantly alter the effects of
             pyrilamine on the RAM. In summary, the therapeutic effect of
             clozapine in reversing PPI impairment was mimicked by the
             H(1) antagonist pyrilamine, while pyrilamine had a mixed
             effect on cognition. Pyrilamine impaired working memory but
             improved reference memory in rats. Thus, H(1) antagonism
             seems to play a role in part of the beneficial actions of
             antipsychotics, such as clozapine.},
   Doi = {10.1016/j.pbb.2007.02.014},
   Key = {fds274243}
}

@article{fds274241,
   Author = {Levin, ED and Caldwell, DP and Perraut, C},
   Title = {Clozapine treatment reverses dizocilpine-induced deficits of
             pre-pulse inhibition of tactile startle response.},
   Journal = {Pharmacology, Biochemistry, and Behavior},
   Volume = {86},
   Number = {3},
   Pages = {597-605},
   Year = {2007},
   Month = {March},
   ISSN = {0091-3057},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/17355891},
   Abstract = {Pre-pulse inhibition (PPI) is a phenomenon of
             neurobehavioral plasticity in which the motor response to a
             startling sensory stimulus is inhibited by a preceding
             sensory stimulus of a lower intensity. The current
             experiment used tactile startle rather than acoustic startle
             to determine the generality of PPI across sensory
             modalities. PPI is easily modeled in experimental animals
             and serves as a useful method for determining the neural
             bases for sensorimotor plasticity, which can be disturbed in
             sensory modulation disorders. In the current study, female
             Sprague-Dawley rats were tested for tactile startle PPI
             after an auditory pre-pulse. The glutamate NMDA receptor
             antagonist dizocilpine (MK-801, 0.05 mg/kg) caused a nearly
             total blockade of the PPI effect (p<0.0005). The
             antipsychotic drug clozapine (1.25 mg/kg, p<0.001 and 2.5
             mg/kg p<0.05) significantly attenuated the
             dizocilpine-induced PPI impairment. Interestingly, the lower
             clozapine dose did not by self enhance PPI and the higher
             clozapine dose when given alone caused a significant
             (p<0.05) PPI impairment relative to control. Nicotine (0.2
             and 0.4 mg/kg) did not significantly interact with the other
             treatments, though the higher nicotine dose did show a trend
             toward attenuating the PPI impairment caused by the high
             clozapine dose. These effects were replicated in a second
             experiment of clozapine-dizocilpine interactions without
             nicotine treatment. This study shows that PPI of tactile
             startle is dramatically impaired by blocking NMDA activation
             and that the prototypic atypical antipsychotic drug
             clozapine can correct this deficit. This may be relevant to
             the action of clozapine in attenuating sensory gating
             deficits in schizophrenia and may point to new avenues of
             treatment for sensory modulation disorders in which there is
             excessive tactile response.},
   Doi = {10.1016/j.pbb.2007.02.005},
   Key = {fds274241}
}

@article{fds274240,
   Author = {Matta, SG and Balfour, DJ and Benowitz, NL and Boyd, RT and Buccafusco,
             JJ and Caggiula, AR and Craig, CR and Collins, AC and Damaj, MI and Donny,
             EC and Gardiner, PS and Grady, SR and Heberlein, U and Leonard, SS and Levin, ED and Lukas, RJ and Markou, A and Marks, MJ and McCallum, SE and Parameswaran, N and Perkins, KA and Picciotto, MR and Quik, M and Rose,
             JE and Rothenfluh, A and Schafer, WR and Stolerman, IP and Tyndale, RF and Wehner, JM and Zirger, JM},
   Title = {Guidelines on nicotine dose selection for in vivo
             research.},
   Journal = {Psychopharmacology},
   Volume = {190},
   Number = {3},
   Pages = {269-319},
   Year = {2007},
   Month = {February},
   ISSN = {0033-3158},
   url = {http://dx.doi.org/10.1007/s00213-006-0441-0},
   Abstract = {RATIONALE: This review provides insight for the judicious
             selection of nicotine dose ranges and routes of
             administration for in vivo studies. The literature is
             replete with reports in which a dosaging regimen chosen for
             a specific nicotine-mediated response was suboptimal for the
             species used. In many cases, such discrepancies could be
             attributed to the complex variables comprising
             species-specific in vivo responses to acute or chronic
             nicotine exposure. OBJECTIVES: This review capitalizes on
             the authors' collective decades of in vivo nicotine
             experimentation to clarify the issues and to identify the
             variables to be considered in choosing a dosaging regimen.
             Nicotine dose ranges tolerated by humans and their animal
             models provide guidelines for experiments intended to
             extrapolate to human tobacco exposure through cigarette
             smoking or nicotine replacement therapies. Just as important
             are the nicotine dosaging regimens used to provide a
             mechanistic framework for acquisition of drug-taking
             behavior, dependence, tolerance, or withdrawal in animal
             models. RESULTS: Seven species are addressed: humans,
             nonhuman primates, rats, mice, Drosophila, Caenorhabditis
             elegans, and zebrafish. After an overview on nicotine
             metabolism, each section focuses on an individual species,
             addressing issues related to genetic background, age, acute
             vs chronic exposure, route of administration, and behavioral
             responses. CONCLUSIONS: The selected examples of successful
             dosaging ranges are provided, while emphasizing the
             necessity of empirically determined dose-response
             relationships based on the precise parameters and conditions
             inherent to a specific hypothesis. This review provides a
             new, experimentally based compilation of species-specific
             dose selection for studies on the in vivo effects of
             nicotine.},
   Doi = {10.1007/s00213-006-0441-0},
   Key = {fds274240}
}

@article{fds274239,
   Author = {Levin, ED and Bencan, Z and Cerutti, DT},
   Title = {Anxiolytic effects of nicotine in zebrafish.},
   Journal = {Physiology & Behavior},
   Volume = {90},
   Number = {1},
   Pages = {54-58},
   Year = {2007},
   Month = {January},
   ISSN = {0031-9384},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/17049956},
   Abstract = {Anxiolytic effects of nicotine have been documented in
             studies with rodents and humans. Understanding the neural
             basis of nicotine-induced anxiolysis can help both with
             developing better aids for smoking cessation as well as with
             the potential development of novel nicotinic ligands for
             treating anxiety. Complementary non-mammalian models may be
             useful for determining the molecular bases of nicotine
             effects on neurobehavioral function. The current project
             examined whether a zebrafish model of anxiety would be
             sensitive to nicotine. When zebrafish are placed in a novel
             environment, they dive to the bottom of the tank. In the
             wild, diving could help to escape predation. We tested the
             anxiolytic effect of nicotine on the novelty-elicited diving
             response and subsequent habituation. Zebrafish placed in a
             novel tank spent the majority of time at the bottom third of
             the tank during the first minute of a 5-min session and then
             show a gradual decrease in time spent at the tank bottom.
             Nicotine treatment at 100 mg/l for 3 min by immersion before
             testing caused a significant decrease in diving throughout
             the session, while 50 mg/l was effective during the first
             minute when the greatest bottom dwelling was seen in
             controls. Nicotine effects were reversed by the nicotinic
             antagonist mecamylamine given together with nicotine, but
             not when administered shortly before the test session after
             prior nicotine dosing. This implies that the effect of
             nicotine on diving was due to net stimulation at nicotinic
             receptors, an effect that is blocked by mecamylamine; and
             that once invoked, this effect is no longer dependent on
             continuing activation of nicotinic receptors. The effect of
             nicotine on diving did not seem to be the result of a
             general disorientation of the fish. The 100 mg/ml nicotine
             dose was shown in our earlier study to significantly improve
             spatial-discrimination learning in zebrafish.
             Nicotine-induced anxiolytic effects can be modeled in the
             zebrafish. This preparation will help in the investigation
             of the molecular bases of this effect.},
   Doi = {10.1016/j.physbeh.2006.08.026},
   Key = {fds274239}
}

@article{fds274238,
   Author = {Rezvani, AH and Overstreet, DH and Levin, ED and Rosenthal, DI and Kordik, CP and Reitz, AB and Vaidya, AH},
   Title = {Effects of atypical anxiolytic N-phenyl-2-[1-[3-(2-pyridinylethynyl)benzoyl]-4-piperidine]acetamide
             (JNJ-5234801) on alcohol intake in alcohol-preferring P
             rats.},
   Journal = {Alcoholism, Clinical and Experimental Research},
   Volume = {31},
   Number = {1},
   Pages = {57-63},
   Year = {2007},
   Month = {January},
   ISSN = {0145-6008},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/17207102},
   Abstract = {BACKGROUND: N-Phenyl-2-[1-[3-(2-pyridinylethynyl)benzoyl]-4-piperidine]acetamide
             (JNJ-5234801) is a structurally novel atypical anxiolytic
             with an overall in vivo profile in animals suggestive of the
             potential to show anxiolytic efficacy in humans at doses
             that will not cause CNS-related side effects. Furthermore,
             unlike the benzodiazepines, JNJ-5234801 does not have an
             adverse interaction with ethanol even at doses 20 to 40
             times the minimal effective dose in the rat elevated plus
             maze (MED=1.0 mg/kg, p.o.). METHODS: In the present study,
             JNJ-5234801 was evaluated for potential efficacy in reducing
             alcohol intake in alcohol-preferring rats.
             Alcohol-preferring P rats were allowed to drink water or
             alcohol (10%, v/v) in a 2-bottle choice procedure. Once
             stable baselines were established, the acute effects of
             JNJ-5234801 [(10-40 mg/kg, intraperitoneally (i.p.)] were
             assessed. In a separate study, chronic treatment with
             JNJ-5234801 (40 mg/kg once daily, i.p.) for 12 consecutive
             days was compared with naltrexone (20 mg/kg, twice daily,
             i.p.). RESULTS: There was a selective dose-dependent
             reduction in alcohol intake in the alcohol-preferring (P)
             rats after acute administration of JNJ-5234801 (10-40 mg/kg,
             i.p.). There were no significant effects on food or water
             intake. When administered subchronically, both JNJ-5234801
             (40 mg/kg once daily, i.p.) and naltrexone (20 mg/kg, twice
             daily, i.p.) considerably reduced alcohol intake, but
             tolerance to the alcohol-suppressing effects appeared to
             occur sooner in the naltrexone-treated group. While both
             compounds slightly but significantly reduced food intake at
             the beginning, only JNJ-5234801 increased water intake and
             decreased alcohol preference. CONCLUSIONS: The novel
             atypical anxiolytic JNJ-5234801 has a favorable profile
             effects on alcohol intake and related measures compared with
             naltrexone, which is recommended for the treatment of
             alcoholism.},
   Doi = {10.1111/j.1530-0277.2006.00264.x},
   Key = {fds274238}
}

@article{fds274234,
   Author = {McClernon, FJ and Hiott, FB and Westman, EC and Rose, JE and Levin,
             ED},
   Title = {Transdermal nicotine attenuates depression symptoms in
             nonsmokers: a double-blind, placebo-controlled
             trial.},
   Journal = {Psychopharmacology},
   Volume = {189},
   Number = {1},
   Pages = {125-133},
   Year = {2006},
   Month = {November},
   ISSN = {0033-3158},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/16977477},
   Abstract = {RATIONALE: Despite established links between nicotine
             dependence and depression, little research has examined the
             effects of nicotine on depression symptoms. OBJECTIVE: This
             study evaluated the acute and chronic effects of transdermal
             nicotine in nonsmokers with baseline depression symptoms
             during a 4-week, double-blind, placebo-controlled trial.
             METHODS: Nonsmokers with scores >or=10 on the Center for
             Epidemiological Studies Depression scale (CES-D) were
             recruited from the community. Mood and cognitive performance
             were measured at baseline (day 0) and at 1, 8, 21, and 28
             days. Participants were randomly assigned to wear a placebo
             or nicotine patch for 4 weeks (3.5 mg/day during weeks 1 and
             4; 7 mg/day during weeks 2 and 3). The final sample
             consisted of 11 nonsmokers with a mean baseline CES-D score
             of 27.36 (SD=10.53). RESULTS: Salivary nicotine levels
             indicated the majority of participants were compliant with
             treatment. Acute nicotine did not alter mood. After
             adjusting for baseline values, chronic nicotine resulted in
             a significant decline in CES-D scores at day 8 (3.5 mg/day),
             but returned to placebo levels by the last visit. This
             return to baseline levels was coincident with a decrease in
             nicotine administration from 7 to 3.5 mg/day. A similar
             trend for improved response inhibition as measured by the
             Conners Continuous Performance Task was also observed.
             Reported side effects were infrequent and minimal.
             CONCLUSION: These findings suggest a role for nicotinic
             receptor systems in the pathophysiology of depression and
             that nicotinic compounds should be evaluated for treating
             depression symptoms.},
   Doi = {10.1007/s00213-006-0516-y},
   Key = {fds274234}
}

@article{fds274235,
   Author = {Levin, ED and Pang, WG and Harrison, J and Williams, P and Petro, A and Ramsdell, JS},
   Title = {Persistent neurobehavioral effects of early postnatal domoic
             acid exposure in rats.},
   Journal = {Neurotoxicology and Teratology},
   Volume = {28},
   Number = {6},
   Pages = {673-680},
   Year = {2006},
   Month = {November},
   ISSN = {0892-0362},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/17046199},
   Abstract = {Domoic acid (DA) is a marine biotoxin, produced by the
             diatom Pseudo-nitzchia spp., which has been shown to cause
             cognitive impairment in adults who are exposed via
             contaminated seafood. The neurobehavioral consequences of
             developmental exposure are much less well understood. In a
             previous study, we showed that a single prenatal exposure to
             DA in rats at mid-gestation caused neurobehavioral changes
             that persist into adulthood including increased
             susceptibility to the benchmark amnestic drug scopolamine.
             In the current study, we examined the lasting
             neurobehavioral consequences of DA exposure on the first day
             of postnatal life, a time in rats marking the completion of
             the major phase of neuroproliferation and corresponding to
             week 24 of human gestation. The effects of DA exposure at
             doses from 0.025-0.1 mg/kg (s.c.) twice per day on each of
             postnatal days 1 and 2 were compared with vehicle-treated
             controls and rats treated by the same protocol with 1 mg/kg
             of kainic acid. Following kainic acid exposure, a
             sex-selective effect was seen with females but not males
             showing a significant slowing of response latency in the
             radial-arm maze. The high DA dose of 0.1 mg/kg was quite
             toxic causing lethality in all of the offspring exposed and
             this group was excluded from further analysis. When the
             offspring in the 0.05 mg/kg DA dose group were tested,
             significant hypoactivity in the Figure-8 maze was observed
             during adolescence. No significant DA effects were seen in
             response latency or choice accuracy on the radial-arm maze
             during either acquisition or with challenge of the amnestic
             drug scopolamine. Early postnatal DA exposure in the rat can
             be lethal and sublethal exposure can cause neurobehavioral
             effects manifest in modest hypoactivity during the
             adolescent period. However, the sublethal persistent
             neurobehavioral toxicity appears to be less pervasive than
             reported effects following DA administered
             mid-gestation.},
   Doi = {10.1016/j.ntt.2006.08.005},
   Key = {fds274235}
}

@article{fds274236,
   Author = {Levin, ED and Lawrence, S and Petro, A and Horton, K and Seidler, FJ and Slotkin, TA},
   Title = {Increased nicotine self-administration following prenatal
             exposure in female rats.},
   Journal = {Pharmacology, Biochemistry, and Behavior},
   Volume = {85},
   Number = {3},
   Pages = {669-674},
   Year = {2006},
   Month = {November},
   ISSN = {0091-3057},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/17196243},
   Abstract = {There is a significant association between maternal
             cigarette smoking during pregnancy and greater subsequent
             risk of smoking in female offspring. In animal models,
             prenatal nicotine exposure causes persistent alterations in
             cholinergic and monoaminergic systems, both of which are
             important for nicotine actions underlying tobacco addiction.
             Accordingly, the current study was conducted to determine if
             there is a cause-and-effect relationship between prenatal
             nicotine exposure and nicotine self-administration starting
             in adolescence. Pregnant rats were administered nicotine (6
             mg/kg/day) by osmotic minipump infusion throughout gestation
             and then, beginning in adolescence and continuing into
             adulthood, female offspring were given access to nicotine
             via a standard operant IV self-administration procedure
             (0.03 mg/kg/infusion). Gestational nicotine exposure did not
             alter the initial rate of nicotine self-administration.
             However, when animals underwent one week of forced
             abstinence and then had a second opportunity to
             self-administer nicotine, the prenatally-exposed animals
             showed a significantly greater rate of self-administration
             than did the controls. Prenatal nicotine exposure causes
             increased nicotine self-administration, which is revealed
             only when the animals are allowed to experience a period of
             nicotine abstinence. This supports a cause-and-effect
             relationship between the higher rates of smoking in the
             daughters of women who smoke cigarettes during pregnancy and
             implicates a role for nicotine in this effect. Our results
             further characterize the long-term liabilities of maternal
             smoking but also point to the potential liabilities of
             nicotine-based treatments for smoking cessation during
             pregnancy.},
   Doi = {10.1016/j.pbb.2006.11.006},
   Key = {fds274236}
}

@article{fds274237,
   Author = {Pocivavsek, A and Icenogle, L and Levin, ED},
   Title = {Ventral hippocampal alpha7 and alpha4beta2 nicotinic
             receptor blockade and clozapine effects on memory in female
             rats.},
   Journal = {Psychopharmacology},
   Volume = {188},
   Number = {4},
   Pages = {597-604},
   Year = {2006},
   Month = {November},
   ISSN = {0033-3158},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/16715255},
   Abstract = {RATIONALE: Nicotinic systems in the hippocampus play
             important roles in memory function. Decreased hippocampal
             nicotinic receptor concentration is associated with
             cognitive impairment in schizophrenia and Alzheimer's
             disease. METHODS: We modeled in rats the cognitive effects
             of chronic decrease in hippocampal alpha7 or alpha4beta2
             receptors with 4-week continuous bilateral local infusions
             of the alpha7 nicotinic antagonist methyllycaconitine (MLA)
             or the alpha4beta2 antagonist dihydro-beta-erythroidine
             (DHbetaE). The working memory effects of these infusions
             were assessed by performance on the radial-arm maze. To test
             the effect of antipsychotic medication, we gave acute
             injections of clozapine and to determine the impact of
             nicotine, which is widely used by people with schizophrenia
             approximately half of the rats received chronic systemic
             infusions of nicotine. RESULTS: Chronic ventral hippocampal
             DHbetaE infusion caused a significant (p < 0.001) working
             memory impairment. Acute systemic clozapine (2.5 mg/kg)
             caused a significant (p < 0.005) working memory impairment
             in rats given control aCSF hippocampal infusions. Clozapine
             significantly (p < 0.025) attenuated the memory deficit
             caused by chronic hippocampal DHbetaE infusions. Chronic
             ventral hippocampal infusions with MLA did not significantly
             affect the working memory performance in the radial-arm
             maze, but it did significantly (p < 0.05) potentiate the
             memory impairment caused by 1.25 mg/kg of clozapine. Chronic
             systemic nicotine did not significantly interact with these
             effects. CONCLUSIONS: The state of nicotinic receptor
             activation in the ventral hippocampus significantly affected
             the impact of clozapine on working memory with blockade of
             alpha7 nicotinic receptors potentiating clozapine-induced
             memory impairment and blockade of alpha4beta2 receptors
             reversing the clozapine effect from impairing to improving
             memory.},
   Doi = {10.1007/s00213-006-0416-1},
   Key = {fds274237}
}

@article{fds274233,
   Author = {Slotkin, TA and Tate, CA and Ryde, IT and Levin, ED and Seidler,
             FJ},
   Title = {Organophosphate insecticides target the serotonergic system
             in developing rat brain regions: disparate effects of
             diazinon and parathion at doses spanning the threshold for
             cholinesterase inhibition.},
   Journal = {Environmental Health Perspectives},
   Volume = {114},
   Number = {10},
   Pages = {1542-1546},
   Year = {2006},
   Month = {October},
   ISSN = {0091-6765},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/17035140},
   Abstract = {BACKGROUND: In the developing brain, serotonin (5HT) systems
             are among the most sensitive to disruption by
             organophosphates. OBJECTIVES: We exposed neonatal rats to
             daily doses of diazinon or parathion on postnatal days
             (PND)1-4 and evaluated 5HT receptors and the 5HT transporter
             in brainstem and forebrain on PND5, focusing on doses of
             each agent below the maximum tolerated dose and spanning the
             threshold for cholinesterase inhibition: 0.5, 1, or 2 mg/kg
             for diazinon, and 0.02, 0.05, and 0.1 mg/kg for parathion.
             RESULTS: Diazinon evoked up-regulation of 5HT1A and 5HT2
             receptor expression even at doses devoid of effects on
             cholinesterase activity, a pattern similar to that seen
             earlier for another organophosphate, chlorpyrifos. In
             contrast, parathion decreased 5HT1A receptors, again at
             doses below those required for effects on cholinesterase.
             The two agents also differed in their effects on the 5HT
             transporter. Diazinon evoked a decrease in the brainstem and
             an increase in the forebrain, again similar to that seen for
             chlorpyrifos; this pattern is typical of damage of nerve
             terminals and reactive sprouting. Parathion had smaller,
             nonsignificant effects. CONCLUSIONS: Our results buttress
             the idea that, in the developing brain, the various
             organophosphates target specific neurotransmitter systems
             differently from each other and without the requirement for
             cholinesterase inhibition, their supposed common mechanism
             of action.},
   Doi = {10.1289/ehp.9337},
   Key = {fds274233}
}

@article{fds274232,
   Author = {Levin, ED and Caldwell, DP},
   Title = {Low-dose mecamylamine improves learning of rats in the
             radial-arm maze repeated acquisition procedure.},
   Journal = {Neurobiology of Learning and Memory},
   Volume = {86},
   Number = {1},
   Pages = {117-122},
   Year = {2006},
   Month = {July},
   ISSN = {1074-7427},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/16632386},
   Abstract = {The nicotinic antagonist mecamylamine has been widely shown
             to cause cognitive impairment. However, these effects are
             mainly seen with high doses. There have been scattered
             findings that low doses of mecamylamine can have the
             opposite effect. This may be due to opposite effects of low
             doses of mecamylamine. In the current study, an extensive
             dose-effect function of mecamylamine was characterized in
             the low-dose range. Adult female Sprague-Dawley rats were
             trained on a repeated acquisition procedure on an automated
             8-arm radial maze. Three of the eight arms were designated
             as correct for any particular session. Five trials per
             session were run. The number of errors per trial to find the
             three correct arms was determined. The rats were trained on
             the repeated acquisition procedure for at least 18 sessions
             at which time they showed reliable learning each session.
             Then, the effect of low doses of mecamylamine between 0 and
             1 mg/kg were assessed in a repeated measures counterbalanced
             design. This dose range of mecamylamine did not affect
             performance on the first trial when the rats were naïve to
             the array to be learned. On trials 2-5 a significant
             (p<.025) quadratic dose-effect function was seen over this
             dose range. The most substantial effect was seen with 0.125
             mg/kg of mecamylamine, which caused a significant (p<.05)
             improvement relative to the saline control condition. The
             effect diminished with increasing mecamylamine doses and
             with the 1 mg/kg dose choice accuracy was back to control
             levels. This study showed that low doses of mecamylamine can
             effectively improve learning. A U-shaped dose-effect curve
             was documented. This suggests possible low-dose nicotinic
             antagonist lines of treatment for cognitive
             impairment.},
   Doi = {10.1016/j.nlm.2006.01.007},
   Key = {fds274232}
}

@article{fds274230,
   Author = {Schmajuk, NA and Larrauri, JA and Hagenbuch, N and Levin, ED and Feldon,
             J and Yee, BK},
   Title = {Startle and prepulse inhibition as a function of background
             noise: a computational and experimental analysis.},
   Journal = {Behavioural Brain Research},
   Volume = {170},
   Number = {2},
   Pages = {182-196},
   Year = {2006},
   Month = {June},
   ISSN = {0166-4328},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/16569445},
   Abstract = {Schmajuk and Larrauri [Schmajuk NA, Larrauri JA. Neural
             network model of prepulse inhibition. Behav Neurosci
             2005;119:1546-62.] introduced a real-time model of acoustic
             startle, prepulse inhibition (PPI) and facilitation (PPF) in
             animals and humans. The model assumes that (1) positive
             values of changes in noise level activate an excitatory and
             a facilitatory pathway, and (2) absolute values of changes
             in noise level activate an inhibitory pathway. The model
             describes many known properties of the phenomena and the
             effect of brain lesions on startle, PPI, and PPF. The
             purpose of the present study is to (a) establish the
             magnitude of startle and PPI as a function of pulse,
             prepulse, and background intensity, and (b) test the model
             predictions regarding an inverted-U function that relates
             startle to the intensity of the background
             noise.},
   Doi = {10.1016/j.bbr.2006.02.021},
   Key = {fds274230}
}

@article{fds274231,
   Author = {Slotkin, TA and Levin, ED and Seidler, FJ},
   Title = {Comparative developmental neurotoxicity of organophosphate
             insecticides: effects on brain development are separable
             from systemic toxicity.},
   Journal = {Environmental Health Perspectives},
   Volume = {114},
   Number = {5},
   Pages = {746-751},
   Year = {2006},
   Month = {May},
   ISSN = {0091-6765},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/16675431},
   Abstract = {A comparative approach to the differences between systemic
             toxicity and developmental neurotoxicity of organophosphates
             is critical to determine the degree to which multiple
             mechanisms of toxicity carry across different members of
             this class of insecticides. We contrasted neuritic outgrowth
             and cholinergic synaptic development in neonatal rats given
             different organophosphates (chlorpyrifos, diazinon,
             parathion) at doses spanning the threshold for impaired
             growth and viability. Animals were treated daily on
             postnatal days 1-4 by subcutaneous injection so as to bypass
             differences in first-pass activation to the oxon or
             catabolism to inactive products. Evaluations occurred on day
             5. Parathion (maximum tolerated dose, 0.1 mg/kg) was far
             more systemically toxic than was chlorpyrifos or diazinon
             (maximum tolerated dose, 1-5 mg/kg). Below the maximum
             tolerated dose, diazinon impaired neuritic outgrowth in the
             forebrain and brainstem, evidenced by a deficit in the ratio
             of membrane protein to total protein. Diazinon also
             decreased choline acetyltransferase activity, a cholinergic
             neuronal marker, whereas it did not affect hemicholinium-3
             binding to the presynaptic choline transporter, an index of
             cholinergic neuronal activity. There was no
             m(subscript)2(/subscript)-muscarinic acetylcholine receptor
             down-regulation, as would have occurred with chronic
             cholinergic hyperstimulation. The same pattern was found
             previously for chlorpyrifos. In contrast, parathion did not
             elicit any of these changes at its maximum tolerated dose.
             These results indicate a complete dichotomy between the
             systemic toxicity of organophosphates and their propensity
             to elicit developmental neurotoxicity. For parathion, the
             threshold for lethality lies below that necessary for
             adverse effects on brain development, whereas the opposite
             is true for chlorpyrifos and diazinon.},
   Doi = {10.1289/ehp.8828},
   Key = {fds274231}
}

@article{fds274228,
   Author = {Nott, A and Levin, ED},
   Title = {Dorsal hippocampal alpha7 and alpha4beta2 nicotinic
             receptors and memory.},
   Journal = {Brain Research},
   Volume = {1081},
   Number = {1},
   Pages = {72-78},
   Year = {2006},
   Month = {April},
   ISSN = {0006-8993},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/16556437},
   Abstract = {Nicotinic receptor systems have been shown to be important
             for working memory. In general, nicotinic agonists have been
             shown to improve memory, and nicotinic antagonists impair
             it. All of the neuronal substrates for nicotinic involvement
             in memory still remain to be discovered. The amygdala and
             ventral hippocampus have both been found to be important for
             nicotinic involvement in memory function. Local infusion of
             the nicotinic antagonist methyllycaconitine (MLA) to block
             alpha7 nicotinic receptors and dihydro-beta-erythrodine
             (DHbetaE) to block alpha4beta2 nicotinic receptors into the
             basolateral amygdala and the ventral hippocampus have been
             found to impair working memory function, with no additive
             effects being observed. The current project assessed the
             roles of alpha7 and alpha4beta2 nicotinic receptors in the
             dorsal hippocampus for memory function. Adult female
             Sprague-Dawley rats were trained on the 16-arm radial maze.
             The rats (n = 10) had bilateral cannulae implanted into the
             dorsal hippocampus. The rats were given acute infusions of
             DHbetaE (0, 1.69, 3.38, and 6.75 microg/side) and MLA (6.75
             microg/side) alone and in combination in a repeated measures
             counter-balanced design. DHbetaE and MLA infusion into the
             dorsal hippocampus significantly increased working memory
             errors. However, when the two drugs were given in
             combination, an attenuated effect was seen. No significant
             effects of MLA or DHbetaE were seen with reference memory
             errors or response latency. These results confirm the
             importance of alpha4beta2 and alpha7 nicotinic acetylcholine
             receptors in the dorsal hippocampus for appetitively-motivated
             spatial cognitive function.},
   Doi = {10.1016/j.brainres.2006.01.052},
   Key = {fds274228}
}

@article{fds274229,
   Author = {Levin, ED and Perraut, C and Pollard, N and Freedman,
             JH},
   Title = {Metallothionein expression and neurocognitive function in
             mice.},
   Journal = {Physiology & Behavior},
   Volume = {87},
   Number = {3},
   Pages = {513-518},
   Year = {2006},
   Month = {March},
   ISSN = {0031-9384},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/16430929},
   Abstract = {Transition metals have been associated with impaired
             neurological development, and neurobehavioral activity.
             Metallothioneins are central components in the metabolism
             and detoxification of a variety of metals, however, little
             is known concerning their role in cognitive function. To
             determine the role of metallothionein in learning and
             memory, mice with deletions of two metallothionein genes
             (MT-1 and MT-2) were trained on a win-shift task in an 8-arm
             radial maze. The parental strain of mice learned the maze at
             a normal rate over an 18-session acquisition period. In
             contrast, the MT-1/MT-2-null mice, which had a similar
             choice accuracy level at the beginning of training, showed a
             poorer rate of learning during the training period. In
             addition, the MT-1/MT-2-null mice showed significantly less
             choice accuracy than the parental strain. The MT-1/MT-2-null
             mice also showed a significant hypoactivity during the early
             and middle parts of acquisition training, but they were not
             different from the wildtype controls during the final phase
             of training. Nicotine treatment, which can improve working
             memory, eliminated the impairment associated with the
             deletion of the MT-1 and MT-2 genes in a dose-related
             fashion after acquisition training in the aging adult mice.
             These results suggest that metallothioneins, through there
             roles in metal physiology or cellular protection, are
             involved in spatial learning and memory function.},
   Doi = {10.1016/j.physbeh.2005.11.014},
   Key = {fds274229}
}

@article{fds274224,
   Author = {Levin, ED and McClernon, FJ and Rezvani, AH},
   Title = {Nicotinic effects on cognitive function: behavioral
             characterization, pharmacological specification, and
             anatomic localization.},
   Journal = {Psychopharmacology},
   Volume = {184},
   Number = {3-4},
   Pages = {523-539},
   Year = {2006},
   Month = {March},
   ISSN = {0033-3158},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/16220335},
   Abstract = {RATIONALE: Nicotine has been shown in a variety of studies
             in humans and experimental animals to improve cognitive
             function. Nicotinic treatments are being developed as
             therapeutic treatments for cognitive dysfunction.
             OBJECTIVES: Critical for the development of nicotinic
             therapeutics is an understanding of the neurobehavioral
             bases for nicotinic involvement in cognitive function.
             METHODS: Specific and diverse cognitive functions affected
             by nicotinic treatments are reviewed, including attention,
             learning, and memory. The neural substrates for these
             behavioral actions involve the identification of the
             critical pharmacologic receptor targets, in particular brain
             locations, and how those incipient targets integrate with
             broader neural systems involved with cognitive function.
             RESULTS: Nicotine and nicotinic agonists can improve working
             memory function, learning, and attention. Both alpha4beta2
             and alpha7 nicotinic receptors appear to be critical for
             memory function. The hippocampus and the amygdala in
             particular have been found to be important for memory, with
             decreased nicotinic activity in these areas impairing
             memory. Nicotine and nicotinic analogs have shown promise
             for inducing cognitive improvement. Positive therapeutic
             effects have been seen in initial studies with a variety of
             cognitive dysfunctions, including Alzheimer's disease,
             age-associated memory impairment, schizophrenia, and
             attention deficit hyperactivity disorder. CONCLUSIONS:
             Discovery of the behavioral, pharmacological, and anatomic
             specificity of nicotinic effects on learning, memory, and
             attention not only aids the understanding of nicotinic
             involvement in the basis of cognitive function, but also
             helps in the development of novel nicotinic treatments for
             cognitive dysfunction. Nicotinic treatments directed at
             specific receptor subtypes and nicotinic cotreatments with
             drugs affecting interacting transmitter systems may provide
             cognitive benefits most relevant to different syndromes of
             cognitive impairment such as Alzheimer's disease,
             schizophrenia, and attention deficit hyperactivity disorder.
             Further research is necessary in order to determine the
             efficacy and safety of nicotinic treatments of these
             cognitive disorders.},
   Doi = {10.1007/s00213-005-0164-7},
   Key = {fds274224}
}

@article{fds274225,
   Author = {Rezvani, AH and Caldwell, DP and Levin, ED},
   Title = {Chronic nicotine interactions with clozapine and risperidone
             and attentional function in rats.},
   Journal = {Progress in Neuro Psychopharmacology & Biological
             Psychiatry},
   Volume = {30},
   Number = {2},
   Pages = {190-197},
   Year = {2006},
   Month = {March},
   ISSN = {0278-5846},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/16310917},
   Abstract = {Although antipsychotic drugs are therapeutically effective
             in attenuating the hallmark symptoms of schizophrenia, these
             improvements do not return most patients to normative
             standards of cognitive function. Thus, complementary drug
             treatment may be needed to treat the attentional deficits of
             schizophrenia as well as to counteract the potential
             attentional impairments caused by some antipsychotic drugs.
             Nicotine, a drug commonly self-administered by a great
             majority of individuals with schizophrenia, has been shown
             to significantly improve cognitive function in some studies.
             The current study was conducted to determine the interactive
             effects of the atypical antipsychotic drugs clozapine and
             risperidone with chronic nicotine administration on
             attentional performance. Adult female Sprague-Dawley rats
             (N=35) were trained to perform an attentional task using an
             operant visual signal detection task. After training, rats
             were infused with a dose of 5 mg/kg/day (s.c.) nicotine base
             (n=18) or saline (n=17) for 28 consecutive days via osmotic
             pump. In Exp. 1, while being administered chronic nicotine
             or saline, rats were given acute doses of clozapine (0,
             0.625, 1.25 and 2.5 mg/kg, s.c.) and were tested for
             attentional function. In Exp. 2, while on chronic nicotine
             or saline, other rats were challenged with acute doses of
             risperidone (0, 0.025, 0.05 and 0.1 mg/kg, s.c.) and were
             tested for attentional function. Results showed that acute
             administration of clozapine caused a significant
             dose-dependent impairment in choice accuracy (percent hit)
             in animals treated with chronic saline. Chronic nicotine
             treatment itself lowered accuracy, but attenuated further
             declines with acute clozapine treatment. Acute
             administration of risperidone at high dose significantly
             reduced performance (percent correct rejection) in
             chronically saline-treated rats, but in a similar fashion as
             in Exp. 1, chronic nicotine lowered accuracy but attenuated
             further impairment with acute risperidone. In summary,
             atypical antipsychotic drugs clozapine and risperidone
             significantly impaired choice accuracy in the visual signal
             detection task. Clozapine was more detrimental than
             risperidone but the adverse effects of both clozapine and
             risperidone on attentional performance were masked in rats
             chronically treated with nicotine.},
   Doi = {10.1016/j.pnpbp.2005.10.017},
   Key = {fds274225}
}

@article{fds274226,
   Author = {Levin, ED and Christopher, NC},
   Title = {Effects of clozapine on memory function in the rat neonatal
             hippocampal lesion model of schizophrenia.},
   Journal = {Progress in Neuro Psychopharmacology & Biological
             Psychiatry},
   Volume = {30},
   Number = {2},
   Pages = {223-229},
   Year = {2006},
   Month = {March},
   ISSN = {0278-5846},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/16356617},
   Abstract = {Clozapine is an effective atypical antipsychotic drug used
             to treat schizophrenia. It has the advantage of producing
             fewer extrapyramidal motor side effects than typical
             antipsychotic drugs such as haloperidol. Schizophrenia
             involves more than the hallmark symptom of psychosis.
             Substantial cognitive impairment is also seen. Effective
             drug treatments against the cognitive impairment of
             schizophrenia need to be developed. The current study was
             conducted to determine the effects of clozapine on working
             memory in the rat neonatal hippocampal lesion model of
             schizophrenia, which includes symptoms of cognitive
             impairment. Infant Sprague-Dawley rats were given ibotenic
             acid lesions of the hippocampus on day 7 of age (using the
             day of birth as day 0). Controls were given vehicle
             infusions. In adulthood, the rats were trained on the 8-arm
             radial maze using the win-shift procedure. After 6 sessions
             of training, the lesioned rats and their controls were
             administered repeated injections of saline or clozapine (2.5
             mg/kg) for the next 12 sessions of training. The females had
             significant radial-arm maze choice accuracy impairments
             caused by either clozapine or the hippocampal lesion, but
             the combination of the two treatments had no additive
             effect. The males showed a different pattern of effects.
             Intact males did not show a significant clozapine-induced
             impairment, whereas males with hippocampal lesions did show
             significant clozapine-induced impairment although
             hippocampal lesions by themselves did not significantly
             impair male choice accuracy. These data show that clozapine
             can cause memory impairment and it potentiates rather than
             reverses hippocampal lesion-induced deficits. There are
             critical sex-related differences in these
             effects.},
   Doi = {10.1016/j.pnpbp.2005.10.018},
   Key = {fds274226}
}

@article{fds274227,
   Author = {Levin, ED and Limpuangthip, J and Rachakonda, T and Peterson,
             M},
   Title = {Timing of nicotine effects on learning in
             zebrafish.},
   Journal = {Psychopharmacology},
   Volume = {184},
   Number = {3-4},
   Pages = {547-552},
   Year = {2006},
   Month = {March},
   ISSN = {0033-3158},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/16175402},
   Abstract = {RATIONALE: Nicotine has been shown in many, but not all,
             studies to improve cognitive function in a number of species
             including rats, mice, monkeys, and humans. Recently, we have
             found that nicotine also improves memory in zebrafish.
             Nicotinic agonists are being developed as novel treatments
             for Alzheimer's disease and other cognitive impairments.
             OBJECTIVES: In screening the therapeutic potential of novel
             nicotinic agonists, it is important to have a rapid assay of
             cognitive improvement. Zebrafish can help with this effort.
             METHODS: We have developed a method of rapidly assessing
             spatial position discrimination learning in zebrafish in one
             session of seven trials. We used this method to determine
             the cognitive effects of nicotine. RESULTS: Nicotine (100
             mg/l administered during 3 min of immersion) caused a
             significant improvement in percent correct performance. This
             dose was within the effective range we found to improve the
             choice accuracy performance of zebrafish using the more
             time-intensive delayed spatial alternation procedure.
             Interestingly, the positive effect of nicotine was seen at
             20-40 min postadministration, but not earlier, and declined
             at 80 and 160 min posttreatment. At the 40-min postdosing
             interval, 200 mg/l nicotine was also found to significantly
             improve choice accuracy. Nicotine-induced accuracy
             improvement was reversed by the nicotinic antagonist
             mecamylamine given shortly before testing but not when given
             concurrently with nicotine. CONCLUSIONS: This position
             discrimination procedure in zebrafish effectively
             demonstrated the cognitive-enhancing effects of nicotine.
             This model may be useful in the early screening of novel
             nicotinic compounds for treatment of cognitive
             dysfunction.},
   Doi = {10.1007/s00213-005-0162-9},
   Key = {fds274227}
}

@article{fds274400,
   Author = {Timme-Laragy, AR and Levin, ED and Di Giulio and RT},
   Title = {Developmental and behavioral effects of embryonic exposure
             to the polybrominated diphenylether mixture DE-71 in the
             killifish (Fundulus heteroclitus).},
   Journal = {Chemosphere},
   Volume = {62},
   Number = {7},
   Pages = {1097-1104},
   Year = {2006},
   Month = {February},
   ISSN = {0045-6535},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/16045967},
   Keywords = {Animals • Behavior, Animal • Embryo, Nonmammalian
             • Fundulidae • Maze Learning • Phenyl Ethers
             • Polybrominated Biphenyls • Swimming • Water
             Pollutants, Chemical • drug effects • drug
             effects* • embryology • growth & development*
             • toxicity*},
   Abstract = {Exposures to penta polybrominated diphenylether (PeBDE)
             cause neurobehavioral toxicity in developing mice and rats.
             As levels of these ubiquitous contaminants are increasing in
             the environment, this raises concern that wildlife may also
             suffer such effects, with consequences for their ability to
             catch prey and avoid predators. PeBDE levels in wild-caught
             fish have been steadily escalating over the past fifteen
             years. To our knowledge, behavioral consequences of piscine
             embryonic exposure to PeBDE has not yet been studied. The
             objectives of this investigation were to characterize
             effects on development in an environmentally relevant fish
             model, and test for latent behavioral effects following
             cessation of exposure. Embryos from the estuarine minnow,
             Fundulus heteroclitus, were exposed from day 0-7 post
             fertilization to the industrial PeBDE mixture, DE-71 (0.001
             to 100 microg l(-1)). Embryos were assayed for hatching
             success, development, and microsomal enzyme cytochrome
             P4501A (CYP1A) activity, which was determined by analysis of
             in ovo ethoxy-resorufin-O-deethylase (EROD) activation in
             embryos. Larval fish were assayed for predation ability,
             activity level, and fright response to a simulated predator.
             Juvenile fish were assayed for learning ability in a
             three-chambered fish maze. No induction of embryonic EROD
             activity was observed, nor was a high dose of DE-71 able to
             inhibit EROD activity induced by beta-naphthoflavone. No
             deformities were detected, but a subtle developmental
             asymmetry with respect to tail curvature direction was
             observed, and a hatching delay of up to 4.5 days was noted.
             Behavioral test results suggest that embryonic exposure to
             DE-71 may alter activity level, fright response, predation
             rates, and learning ability in subsequent life
             stages.},
   Doi = {10.1016/j.chemosphere.2005.05.037},
   Key = {fds274400}
}

@article{fds274223,
   Author = {Levin, ED and Rezvani, AH},
   Title = {Nicotinic-antipsychotic drug interactions and cognitive
             function.},
   Journal = {Exs},
   Volume = {98},
   Pages = {185-205},
   Year = {2006},
   ISSN = {1023-294X},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/17019889},
   Abstract = {In summary, neuronal nicotinic systems are important for a
             variety of aspects of cognitive function impacted by
             antipsychotic drugs. It has been demonstrated that
             antipsychotic drugs have memory and attentional impairing
             effects when given to unimpaired subjects. Nicotine can
             reduce some of these impairments, but antipsychotic drug
             administration can also attenuate nicotine effects. We have
             found that nicotinic agonists selective for alpha7 and
             alpha4beta2 receptor subtypes significantly improve learning
             and memory. Serotonergic actions of antipsychotic drugs may
             decrease efficacy of nicotinic co-treatments. When the
             antipsychotic drug clozapine and nicotine are administered
             to subjects with cognitive impairments caused by NMDA
             glutamate receptor blockade or hippocampal dysfunction they
             can significantly attenuate the attentional and memory
             impairments. Nicotine has been shown in our studies to
             reverse the memory impairment caused by acute
             clozapine-induced memory improvement. Acute risperidone and
             haloperidol has been shown to attenuate nicotine-induced
             memory improvement. We have determined the role of
             hippocampal alpha7 and alpha4beta2 nicotinic receptors in
             the neural basis of nicotinic antipsychotic interactions.
             Local acute and chronic hippocampal infusion of either
             nicotinic alpha7 or alpha4beta2 antagonists cause
             significant spatial working memory impairment. Chronic
             hippocampal nicotinic antagonist infusions have served as a
             model of persistent decreases in nicotinic receptor level
             seen in schizophrenia and Alzheimer's disease. Clozapine
             attenuated the memory deficit caused by chronic suppression
             of hippocampal alpha4beta2 receptors while the amnestic
             effects of clozapine were potentiated by chronic suppression
             of hippocampal alpha7 receptors. Nicotinic co-treatment may
             be a useful adjunct in the treatment of schizophrenia, to
             attenuate cognitive impairment of schizophrenia. Nicotine as
             well as selective nicotinic alpha7 and alpha4beta2 receptor
             agonists significantly improve working memory and
             attentional function. Nicotine treatment was found to be
             effective in attenuating the attentional and memory
             impairments caused by the psychototmimetic NMDA antagonist
             dizocilpine (MK-801), a model of the cognitive impairment of
             schizophrenia. Studies of the interactions of antipsychotic
             drugs with nicotinic agents provided quite useful
             information concerning possible co-treatment of people with
             schizophrenia with nicotinic therapy. Nicotine was found to
             significantly attenuate the memory impairments caused by the
             antipsychotic drugs clozapine and olanzapine. Interestingly,
             nicotine-induced cognitive improvement was significantly
             attenuated by the antipsychotic drug clozapine. One of the
             principal effects of clozapine is to block 5HT2 receptors.
             Ketanserin a 5HT2 antagonist significantly attenuated
             nicotine-induced improvements in attention and memory. Thus
             it appears that antipsychotic drugs with actions blocking
             5HT2 receptors may limit the efficacy of nicotinic
             co-treatments for cognitive enhancement.},
   Doi = {10.1007/978-3-7643-7772-4_10},
   Key = {fds274223}
}

@article{fds274339,
   Author = {Levin, ED},
   Title = {The rationale for studying transmitter interactions to
             understand the neural bases of cognitive
             function.},
   Journal = {Exs},
   Volume = {98},
   Pages = {1-3},
   Year = {2006},
   ISSN = {1023-294X},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/17019880},
   Doi = {10.1007/978-3-7643-7772-4_1},
   Key = {fds274339}
}

@article{fds274221,
   Author = {Slikker, W and Xu, ZA and Levin, ED and Slotkin, TA},
   Title = {Mode of action: disruption of brain cell replication, second
             messenger, and neurotransmitter systems during development
             leading to cognitive dysfunction--developmental
             neurotoxicity of nicotine.},
   Journal = {Critical Reviews in Toxicology},
   Volume = {35},
   Number = {8-9},
   Pages = {703-711},
   Year = {2005},
   Month = {October},
   ISSN = {1040-8444},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/16417037},
   Abstract = {Developmental exposure to nicotine in rats results in
             neurobehavioral effects such as reduced locomotor and
             cognitive function. Key events in the animal mode of action
             (MOA) include binding to the nicotinic cholinergic receptor
             during prenatal and/or early postnatal development. This
             leads to premature onset of cell differentiation at the
             expense of cell replication, which leads to brain cell death
             or structural alterations in regional brain areas. Other
             events include an initial increase followed by a decrease in
             adenyl cyclase activity, as well as effects on the
             noradrenergic, dopaminergic, and serotonergic
             neurotransmitter systems. Because the nicotine receptor is
             also present in the developing human brain and the
             underlying biology for DNA synthesis and cell signaling is
             comparable, this MOA is likely to be relevant for humans.
             Although the effects of nicotine exposure in developing
             humans is not well documented, nicotine exposure as a result
             of cigarette smoking during pregnancy is associated with
             several physiological and behavioral outcomes that are
             reminiscent of the effects of nicotine alone in animal
             models. As data become available with the advent of the use
             of the nicotine patch in pregnant humans, the question as to
             the relative importance of smoking per se versus nicotine
             alone may be determined.},
   Doi = {10.1080/10408440591007421},
   Key = {fds274221}
}

@article{fds274222,
   Author = {Levin, E and Icenogle, L and Farzad, A},
   Title = {Ketanserin attenuates nicotine-induced working memory
             improvement in rats.},
   Journal = {Pharmacology, Biochemistry, and Behavior},
   Volume = {82},
   Number = {2},
   Pages = {289-292},
   Year = {2005},
   Month = {October},
   ISSN = {0091-3057},
   url = {http://dx.doi.org/10.1016/j.pbb.2005.08.017},
   Abstract = {Nicotinic systems have been shown in numerous studies to be
             important for spatial working memory. Nicotinic systems are
             certainly not acting alone in the basis of memory function,
             but act in concert with a variety of other neural systems.
             Important for these interactions is nicotinic induced
             release of a variety of neurotransmitters involved in memory
             function including serotonin (5-HT). We have found that the
             5-HT2 receptor antagonist, ketanserin, effectively
             attenuated nicotine-induced attentional improvement. The
             current study explored the interaction between nicotinic and
             serotonergic systems in the performance of a spatial working
             memory task in the radial-arm maze. Female Sprague-Dawley
             rats were trained on the win-shift working memory task on
             the 8-arm radial maze. After 18 sessions of acquisition
             training the rats were given acute doses of nicotine (0.2
             and 0.4 mg/kg), ketanserin (0.5, 1 and 2 mg/kg) or
             combinations of the two. The vehicle served as the control.
             As seen in previous studies, nicotine caused a significant
             improvement in working memory performance as indexed by the
             number of correct arm entries before the first error
             (entries to repeat). Ketanserin at the doses tested did not
             cause a significant effect on choice accuracy, but it did
             significantly attenuate the improvement caused by the 0.2
             mg/kg nicotine dose. The higher 0.4 mg/kg nicotine dose was
             nearly sufficient to overcome the ketanserin effect. This
             study shows that, as with attentional function,
             nicotine-induced working memory improvement is attenuated by
             the 5-HT2 antagonist ketanserin. Given that many
             antipsychotic drugs have substantial 5-HT2 antagonist
             effects, these atypical antipsychotic drugs may reduce the
             cognitive improvements caused by nicotinic
             treatments.},
   Doi = {10.1016/j.pbb.2005.08.017},
   Key = {fds274222}
}

@article{fds274219,
   Author = {Barron, S and White, A and Swartzwelder, HS and Bell, RL and Rodd, ZA and Slawecki, CJ and Ehlers, CL and Levin, ED and Rezvani, AH and Spear,
             LP},
   Title = {Adolescent vulnerabilities to chronic alcohol or nicotine
             exposure: findings from rodent models.},
   Journal = {Alcoholism, Clinical and Experimental Research},
   Volume = {29},
   Number = {9},
   Pages = {1720-1725},
   Year = {2005},
   Month = {September},
   ISSN = {0145-6008},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/16205372},
   Abstract = {This article presents an overview of the proceedings from a
             symposium entitled "Is adolescence special? Possible
             age-related vulnerabilities to chronic alcohol or nicotine
             exposure," organized by Susan Barron and Linda Spear and
             held at the 2004 Research Society on Alcoholism Meeting in
             Vancouver, British Columbia. This symposium, co-sponsored by
             the Fetal Alcohol Syndrome Study Group and the
             Neurobehavioral Teratology Society, focused on our current
             knowledge regarding the long-term consequences of ethanol
             and/or nicotine exposure during adolescence with the
             emphasis on data from rodent models. The support from these
             two societies represents the understanding by these research
             groups that adolescence represents a unique developmental
             stage for the effects of chronic drug exposure and also
             marks an age in which many risky behaviors including alcohol
             consumption and smoking typically begin. The speakers
             included (1) Aaron White, who presented data on the effects
             of adolescent ethanol exposure on subsequent motor or
             cognitive response to an ethanol challenge in adulthood; (2)
             Richard Bell, who presented data suggesting that genetic
             differences could play a role in adolescent vulnerability to
             ethanol; (3) Craig Slawecki, who presented data looking at
             the effects of chronic exposure to alcohol or nicotine on
             neurophysiologic and behavioral end points; and (4) Ed
             Levin, who presented data on acute and long-term
             consequences of adolescent nicotine exposure. Finally, Linda
             Spear provided some summary points and recommendations
             regarding unresolved issues and future directions.},
   Doi = {10.1097/01.alc.0000179220.79356.e5},
   Key = {fds274219}
}

@article{fds274220,
   Author = {Levin, ED},
   Title = {Marine and freshwater toxin impacts on neurobehavioral
             function},
   Journal = {Neurotoxicology and Teratology},
   Volume = {27},
   Number = {5},
   Pages = {693},
   Publisher = {Elsevier BV},
   Year = {2005},
   Month = {September},
   ISSN = {0892-0362},
   url = {http://dx.doi.org/10.1016/j.ntt.2005.06.011},
   Doi = {10.1016/j.ntt.2005.06.011},
   Key = {fds274220}
}

@article{fds274478,
   Author = {Levin, ED and Pizarro, K and Pang, WG and Harrison, J and Ramsdell,
             JS},
   Title = {Persisting behavioral consequences of prenatal domoic acid
             exposure in rats.},
   Journal = {Neurotoxicology and Teratology},
   Volume = {27},
   Number = {5},
   Pages = {719-725},
   Year = {2005},
   Month = {September},
   ISSN = {0892-0362},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/16054336},
   Keywords = {Animals • Behavior, Animal • Exploratory Behavior
             • Female • Kainic Acid • Male • Maze
             Learning • Memory • Motor Activity •
             Muscarinic Antagonists • Neurotoxins • Pregnancy
             • Prenatal Exposure Delayed Effects* • Rats •
             Rats, Sprague-Dawley • Scopolamine Hydrobromide •
             Sex Characteristics • analogs & derivatives* •
             drug effects • drug effects* • pharmacology •
             toxicity • toxicity*},
   Abstract = {To investigate the behavioral effects of prenatal exposure
             to the marine toxin domoic acid, pregnant female rats were
             injected subcutaneously with 0, 0.3, 0.6, or 1.2 mg/kg of
             domoic acid on gestational day 13. The offspring were then
             run through a behavioral testing battery to determine the
             developmental effects of the toxin on spontaneous
             alternation in the T-maze, on locomotor activity in the
             Figure-8 maze, and on working memory in the 8-arm radial
             maze. In the T-maze, no significant domoic acid induced
             differences were seen on spontaneous alternation, but there
             were significant domoic acid effects on latency. Prenatal
             domoic acid exposure caused a dose-related increase in
             response latency in the second spontaneous alternation test.
             There was also a significant domoic acid effect seen in the
             1-h long Figure-8 maze test. Locomotor activity measured in
             the Figure-8 maze detected a persisting effect of the 1.2
             mg/kg domoic acid dose, which significantly increased the
             rate of habituation over the activity test session. This was
             characterized by higher initial activity followed by greater
             decline in activity. In the radial-arm maze the control
             vehicle treated rats showed the normal sex-related
             difference in spatial learning and memory with males
             outperforming females. Developmental domoic acid exposure
             decreased this effect such that the normal sex difference in
             spatial memory was not seen with the 1.2 mg/kg domoic acid
             dose. The rats of both sexes with a history of prenatal
             domoic acid exposure showed increased susceptibility to the
             amnestic effects of the muscarinic acetylcholine
             scopolamine, suggesting that they had less functional
             reserve with which to solve the radial-arm maze memory task.
             This study demonstrates persisting neurobehavioral effects
             of acute prenatal exposure to domoic acid at doses that do
             not cause overt clinical signs of toxicity.},
   Language = {eng},
   Doi = {10.1016/j.ntt.2005.06.017},
   Key = {fds274478}
}

@article{fds274500,
   Author = {Kreider, ML and Levin, ED and Seidler, FJ and Slotkin,
             TA},
   Title = {Gestational dexamethasone treatment elicits sex-dependent
             alterations in locomotor activity, reward-based memory and
             hippocampal cholinergic function in adolescent and adult
             rats.},
   Journal = {Neuropsychopharmacology},
   Volume = {30},
   Number = {9},
   Pages = {1617-1623},
   Year = {2005},
   Month = {September},
   ISSN = {0893-133X},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/15812569},
   Keywords = {Acetylcholine • Age Factors • Analysis of Variance
             • Animals • Animals, Newborn • Antineoplastic
             Agents, Hormonal • Behavior, Animal • Cholinergic
             Agents • Dexamethasone • Female •
             Hemicholinium 3 • Hippocampus • Male • Maze
             Learning • Memory • Motor Activity •
             Pregnancy • Prenatal Exposure Delayed Effects* •
             Protein Binding • Rats • Sex Characteristics*
             • Tritium • adverse effects* • drug effects
             • drug effects* • metabolism* •
             pharmacokinetics},
   Abstract = {Glucocorticoids are the consensus treatment for preventing
             respiratory distress syndrome in preterm infants but there
             is emerging evidence of subsequent neurobehavioral
             abnormalities, independent of somatic growth effects.
             Pregnant rats were given 0.2 mg/kg of dexamethasone, a dose
             commensurate with clinical use, on gestational days 17-19
             and behavioral evaluations were made on the offspring in
             adolescence and adulthood. The dexamethasone groups had the
             same body weights as the controls but nevertheless displayed
             long-term, sex-selective alterations in locomotor and
             cognitive behaviors. In the figure-8 activity apparatus,
             dexamethasone treatment ablated the normal sex differences
             in locomotor activity by reducing values in females to the
             lower level typical of males; habituation of activity
             similarly was impaired in females, reducing the profile to
             match that of control males, while male rats in the
             dexamethasone group showed a partially feminized pattern of
             habituation. In the 8-arm radial maze, control rats
             displayed typical sex differences, with male rats performing
             more accurately than females. Dexamethasone treatment
             eliminated this normal dichotomy, delaying learning in males
             while improving performance in females to the level normally
             seen in control males. Finally, we assessed hippocampal
             [3H]hemicholinium-3 binding as a biomarker for cholinergic
             synaptic activity, and again found loss of sex differences
             in the dexamethasone group: values in males were increased
             to the higher levels typical of females. These results
             indicate that gestational treatment with dexamethasone
             obtunds the normal sex differences in neurochemistry and
             behavior that are typically seen in adolescence in
             adulthood, thus producing sex-selective alterations in
             activity, learning, and memory.},
   Doi = {10.1038/sj.npp.1300716},
   Key = {fds274500}
}

@article{fds274218,
   Author = {Heindel, JJ and Levin, E},
   Title = {Developmental origins and environmental influences--Introduction.
             NIEHS symposium.},
   Journal = {Birth Defects Research. Part A, Clinical and Molecular
             Teratology},
   Volume = {73},
   Number = {7},
   Pages = {469},
   Year = {2005},
   Month = {July},
   url = {http://dx.doi.org/10.1002/bdra.20141},
   Doi = {10.1002/bdra.20141},
   Key = {fds274218}
}

@article{fds274342,
   Author = {Levin, ED},
   Title = {Fetal nicotinic overload, blunted sympathetic responsivity,
             and obesity.},
   Journal = {Birth Defects Research. Part A, Clinical and Molecular
             Teratology},
   Volume = {73},
   Number = {7},
   Pages = {481-484},
   Year = {2005},
   Month = {July},
   ISSN = {1542-0752},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/15959889},
   Keywords = {Adipose Tissue • Animals • Central Nervous System
             • Chlorpyrifos • Energy Metabolism • Female
             • Nicotine • Obesity • Pregnancy •
             Prenatal Exposure Delayed Effects* • Rats •
             Sympathetic Nervous System • Time Factors • Weight
             Gain • adverse effects • adverse effects* •
             drug effects • drug effects* • etiology* •
             metabolism • pharmacology},
   Language = {eng},
   Doi = {10.1002/bdra.20162},
   Key = {fds274342}
}

@article{fds274465,
   Author = {Levin, ED and Christopher, NC and Crapo, JD},
   Title = {Memory decline of aging reduced by extracellular superoxide
             dismutase overexpression.},
   Journal = {Behavior Genetics},
   Volume = {35},
   Number = {4},
   Pages = {447-453},
   Year = {2005},
   Month = {July},
   ISSN = {0001-8244},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/15971025},
   Keywords = {Aging • Animals • Female • Gene Expression
             Profiling • Genotype • Maze Learning • Memory
             Disorders • Mice • Mice, Transgenic •
             Oxidative Stress • Signal Transduction •
             Superoxide Dismutase • biosynthesis* • enzymology
             • genetics* • physiology* •
             physiopathology*},
   Abstract = {Extracellular superoxide dismutase (EC-SOD) plays an
             important role in controlling oxidative stress as well as
             intercellular signaling. In the current study, we tested the
             effect of EC-SOD overexpression over the lifespan of a set
             of mice and their wild-type controls to determine the time
             scale over which EC-SOD overexpression might attenuate
             aging-induced memory impairment. Mice with overexpression of
             EC-SOD and wild-type controls were initially trained on the
             radial-arm maze as young adults (3-5 months) and then
             retrained during middle age (12-14 months) and retested in
             old age at 27 and 30 months. There was little EC-SOD effect
             during the young adult middle age periods. EC-SOD
             overexpression prevented the decline in choice accuracy when
             the mice were 27-30 months of age. The EC-SOD overexpressing
             mice maintained their performance, while the wild-type mice
             declined to naïve levels of performance by 30 months of
             age. Enhancement of EC-SOD activity appears to improve
             memory performance specifically in aging mice. EC-SOD
             mimetic treatment during the course of aging may hold
             promise for aging-induced cognitive impairment.},
   Language = {eng},
   Doi = {10.1007/s10519-004-1510-y},
   Key = {fds274465}
}

@article{fds274439,
   Author = {Addy, NA and Pocivavsek, A and Levin, ED},
   Title = {Reversal of clozapine effects on working memory in rats with
             fimbria-fornix lesions.},
   Journal = {Neuropsychopharmacology},
   Volume = {30},
   Number = {6},
   Pages = {1121-1127},
   Year = {2005},
   Month = {June},
   ISSN = {0893-133X},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/15688087},
   Keywords = {Animals • Antipsychotic Agents • Clozapine •
             Female • Fornix, Brain • Hippocampus • Maze
             Learning • Memory, Short-Term • Nicotine •
             Nicotinic Agonists • Rats • Rats, Sprague-Dawley
             • antagonists & inhibitors • drug effects •
             drug effects* • pharmacology • pharmacology*
             • physiology • physiology*},
   Abstract = {Clozapine is an effective antipsychotic drug, but its
             effects on cognitive function are unclear. Previously, we
             found that clozapine caused a working memory deficit, which
             was reversed by nicotine. Hippocampal systems are important
             in determining clozapine effect on memory. In the current
             study, the memory effects of clozapine and nicotine
             administration were determined in rats with lesions of the
             fimbria-fornix, a fiber bundle which carries cholinergic and
             other projections between the septum and the hippocampus.
             Female Sprague-Dawley rats were trained on a win-shift
             procedure in the radial-arm maze, in which each arm entry
             was rewarded once per session. Then, 13 rats received
             bilateral knife-cut lesions of the fimbria-fornix, while 14
             rats underwent sham surgery. The rats were tested after
             subcutaneous injections with combinations of clozapine (0
             and 1.25 mg/kg) and nicotine (0, 0.2, and 0.4 mg/kg). In
             sham-operated rats, clozapine caused a significant (P<0.005)
             working memory impairment. Fimbria-fornix lesions also
             caused a significant (P<0.05) memory impairment.
             Interestingly, clozapine had the opposite effect on working
             memory in the lesioned vs sham-operated rats. In contrast to
             its effects in controls, clozapine (1.25 mg/kg)
             significantly (P<0.05) attenuated the working memory deficit
             caused by fimbria-fornix lesions. Nicotine (0.2 mg/kg) did
             not quite significantly improve memory in lesioned rats. The
             effects of clozapine and nicotine were not additive in the
             lesioned rats. This study demonstrates the efficacy of
             clozapine in improving working memory in
             fimbria-fornix-lesioned rats, whereas it causes impairments
             in intact rats. Therapeutic treatment with clozapine in
             people with malfunctions of the hippocampus such as seen in
             schizophrenia may improve cognitive performance, whereas the
             same doses of clozapine may impair memory in individuals
             without hippocampal malfunction.},
   Language = {eng},
   Doi = {10.1038/sj.npp.1300669},
   Key = {fds274439}
}

@article{fds274351,
   Author = {Aldridge, JE and Levin, ED and Seidler, FJ and Slotkin,
             TA},
   Title = {Developmental exposure of rats to chlorpyrifos leads to
             behavioral alterations in adulthood, involving serotonergic
             mechanisms and resembling animal models of
             depression.},
   Journal = {Environmental Health Perspectives},
   Volume = {113},
   Number = {5},
   Pages = {527-531},
   Year = {2005},
   Month = {May},
   ISSN = {0091-6765},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/15866758},
   Keywords = {Animals • Animals, Newborn • Behavior, Animal
             • Chlorpyrifos • Cognition Disorders •
             Depression • Disease Models, Animal • Female
             • Injections, Subcutaneous • Insecticides •
             Male • Maze Learning • Memory • Memory
             Disorders • Random Allocation • Rats • Rats,
             Sprague-Dawley • Serotonin • administration &
             dosage • chemically induced* • growth &
             development • physiology • physiopathology •
             toxicity*},
   Abstract = {Developmental exposure to chlorpyrifos (CPF) causes
             persistent changes in serotonergic (5HT) systems. We
             administered 1 mg/kg/day CPF to rats on postnatal days 1-4,
             a regimen below the threshold for systemic toxicity. When
             tested in adulthood, CPF-exposed animals showed
             abnormalities in behavioral tests that involve 5HT
             mechanisms. In the elevated plus maze, males treated with
             CPF spent more time in the open arms, an effect seen with
             5HT deficiencies in animal models of depression. Similarly,
             in an anhedonia test, the CPF-exposed group showed a
             decreased preference for chocolate milk versus water.
             Developmental CPF exposure also has lasting effects on
             cognitive function. We replicated our earlier finding that
             developmental CPF exposure ablates the normal sex
             differences in 16-arm radial maze learning and memory:
             during acquisition training, control male rats typically
             perform more accurately than do control females, but CPF
             treatment eliminated this normal sex difference. Females
             exposed to CPF showed a reduction in working and reference
             memory errors down to the rate of control males. Conversely,
             CPF-exposed males exhibited an increase in working and
             reference memory errors. After radial-arm acquisition
             training, we assessed the role of 5HT by challenging the
             animals with the 5HT2 receptor antagonist ketanserin.
             Ketanserin did not affect performance in controls but
             elicited dose-dependent increases in working and reference
             memory errors in the CPF group, indicating an abnormal
             dependence on 5HT systems. Our results indicate that
             neonatal CPF exposures, classically thought to be subtoxic,
             produce lasting changes in 5HT-related behaviors that
             resemble animal models of depression.},
   Doi = {10.1289/ehp.7867},
   Key = {fds274351}
}

@article{fds274440,
   Author = {Levin, ED and Petro, A and Beatty, A},
   Title = {Olanzapine interactions with nicotine and mecamylamine in
             rats: effects on memory function.},
   Journal = {Neurotoxicology and Teratology},
   Volume = {27},
   Number = {3},
   Pages = {459-464},
   Year = {2005},
   Month = {May},
   ISSN = {0892-0362},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/15939205},
   Keywords = {Animals • Antipsychotic Agents • Benzodiazepines
             • Dose-Response Relationship, Drug • Drug
             Interactions • Female • Maze Learning •
             Mecamylamine • Memory • Memory, Short-Term •
             Nicotine • Nicotinic Agonists • Nicotinic
             Antagonists • Rats • Rats, Sprague-Dawley •
             drug effects • drug effects* •
             pharmacology*},
   Abstract = {Olanzapine is a widely used atypical antipsychotic drug. It
             is quite effective in reducing psychotic symptoms. However,
             the syndrome of schizophrenia encompasses more than
             psychosis. There is a pronounced cognitive impairment among
             other negative neurobehavioral symptoms. Classic
             antipsychotic drugs such as haloperidol do not alleviate
             cognitive impairment associated with schizophrenia and have
             been shown to exacerbate the dysfunction. The atypical
             antipsychotic drugs have a different profile of receptor
             actions and may have a different array of actions on
             cognitive function. The purpose of the current studies was
             to determine the effects of olanzapine on working memory
             function as measured by choice accuracy in the radial-arm
             maze. In determining the cognitive effects of any
             antipsychotic drug it is critical to determine its
             interactions with nicotinic manipulations since the great
             majority of people with schizophrenia smoke cigarettes and
             alterations in nicotinic receptors have been found in people
             with schizophrenia. Olanzapine caused a significant working
             memory impairment. Nicotine attenuated olanzapine-induced
             memory deficits. It may be the case that nicotinic
             co-treatment will be useful in addressing the cognitive
             impairment of schizophrenia.},
   Doi = {10.1016/j.ntt.2005.01.011},
   Key = {fds274440}
}

@article{fds274470,
   Author = {Levin, ED and Petro, A and Caldwell, DP},
   Title = {Nicotine and clozapine actions on pre-pulse inhibition
             deficits caused by N-methyl-D-aspartate (NMDA) glutamatergic
             receptor blockade.},
   Journal = {Progress in Neuro Psychopharmacology & Biological
             Psychiatry},
   Volume = {29},
   Number = {4},
   Pages = {581-586},
   Year = {2005},
   Month = {May},
   ISSN = {0278-5846},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/15866361},
   Keywords = {Animals • Antipsychotic Agents • Clozapine •
             Dizocilpine Maleate • Dose-Response Relationship, Drug
             • Drug Synergism • Excitatory Amino Acid
             Antagonists • Female • Nicotine • Nicotinic
             Agonists • Rats • Rats, Sprague-Dawley •
             Receptors, N-Methyl-D-Aspartate • Startle Reaction
             • antagonists & inhibitors • antagonists &
             inhibitors* • drug effects* • pharmacology •
             pharmacology*},
   Abstract = {Pre-pulse inhibition (PPI) is a phenomenon of
             neurobehavioral plasticity in which the motor response to a
             startling stimulus is inhibited by a preceding stimulus of a
             lower intensity. Most often this is tested in the auditory
             mode. PPI is impaired in a variety of clinical states, most
             notably schizophrenia. PPI is easily modeled in experimental
             animals and serves as a useful basis for determining the
             neural bases for behavioral plasticity. In the current study
             we examined the interactions of N-methyl-D-aspartate (NMDA)
             glutamate and nicotinic cholinergic receptor systems in the
             expression of PPI. Female Sprague-Dawley rats were tested
             for auditory PPI after s.c. injections of the NMDA
             antagonist dizocilpine (also known as MK-801), the
             prototypic nicotinic agonist nicotine or both. Vehicle
             (saline) injections served as the control. Nicotine (0.2-0.8
             mg/kg) by itself caused a modest but significant
             dose-related improvement in PPI. Dizocilpine (25-100
             microg/kg) caused a dramatic dose-related impairment in PPI.
             Interestingly, the low to moderate doses of nicotine
             potentiated the PPI impairment by dizocilpine. In a second
             experiment nicotine and dizocilpine interactions with the
             atypical antipsychotic drug clozapine were assessed. As in
             the first experiment, nicotine potentiated the adverse
             effects of dizocilpine on PPI. The combination of nicotine
             with clozapine effectively attenuated the PPI impairment
             caused by dizocilpine when neither alone was effective.
             Inasmuch as PPI is impaired in schizophrenia, its reversal
             by the antipsychotic drug clozapine may depend on
             co-administration of nicotine by smoking in the patients.
             Development of nicotinic-based co-treatments for
             schizophrenia may achieve this benefit of nicotine without
             the hazards of smoking. Sensory modulation deficit, which is
             a syndrome of sensory over-responsiveness may also benefit
             from such combination therapy.},
   Doi = {10.1016/j.pnpbp.2005.01.012},
   Key = {fds274470}
}

@article{fds274499,
   Author = {Rezvani, AH and Caldwell, DP and Levin, ED},
   Title = {Nicotinic-serotonergic drug interactions and attentional
             performance in rats.},
   Journal = {Psychopharmacology},
   Volume = {179},
   Number = {3},
   Pages = {521-528},
   Year = {2005},
   Month = {May},
   ISSN = {0033-3158},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/15682310},
   Keywords = {Animals • Attention • Dose-Response Relationship,
             Drug • Drug Interactions • Female •
             Ketanserin • Nicotine • Psychomotor Performance
             • Rats • Rats, Sprague-Dawley • Receptor,
             Serotonin, 5-HT2A • Serotonin Antagonists •
             antagonists & inhibitors • drug effects* •
             pharmacology • pharmacology* •
             physiology},
   Abstract = {RATIONALE: Both central serotonergic and nicotinic systems
             play important roles in a variety of neurobehavioral
             functions; however, the interactions of these two systems
             have not been fully characterized. The current study served
             to determine the impact of a relatively selective 5-HT2A
             receptor antagonist, ketanserin, on attentional function in
             rats and the interactions of ketanserin with nicotine
             administration. METHODS: A standard operant visual signal
             detection task was used to assess sustained attention. In
             expt 1, adult female Sprague-Dawley rats (n = 39) were
             injected subcutaneously (SC) with a dose range of ketanserin
             (0, 0.25, 0.5 and 1 mg/kg). In expt 2, the interactions of
             acute ketanserin (0, 1 and 2 mg/kg, SC) and acute nicotine
             (0, 25 and 50 microg/kg, SC) were assessed. In expt 3, the
             interaction of acute ketanserin (0, 1 and 2 mg/kg, SC) and
             chronic nicotine (5 mg/kg per day, SC for 4 weeks via
             osmotic pump) was characterized. Using an operant visual
             signal detection task, three possible outcomes (dependent
             variables) were measured in each trial: percent hit, percent
             correct rejection, and response omissions. RESULTS:
             Ketanserin, when given alone, did not have a significant
             effect on either percent hit or percent correct rejection.
             Acute administration of 25 microg/kg nicotine significantly
             improved percent hit (i.e. improvement in choice accuracy),
             an effect that was reversed by acute administration of 1
             mg/kg ketanserin. Chronic nicotine infusion for 28
             consecutive days significantly increased percent correct
             rejection (i.e. improvement in choice accuracy) without
             development of tolerance, an effect which was reversed by an
             acute dose of 2 mg/kg ketanserin. CONCLUSIONS: These data
             suggest a functional interaction between nicotine and 5-HT2A
             receptor antagonist ketanserin.},
   Doi = {10.1007/s00213-004-2060-y},
   Key = {fds274499}
}

@article{fds274514,
   Author = {Levin, ED and Tizabi, Y and Rezvani, AH and Caldwell, DP and Petro, A and Getachew, B},
   Title = {Chronic nicotine and dizocilpine effects on regionally
             specific nicotinic and NMDA glutamate receptor
             binding.},
   Journal = {Brain Research},
   Volume = {1041},
   Number = {2},
   Pages = {132-142},
   Year = {2005},
   Month = {April},
   ISSN = {0006-8993},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/15829222},
   Keywords = {Allosteric Regulation • Animals • Binding Sites
             • Binding, Competitive • Brain •
             Bungarotoxins • Cystine • Dizocilpine Maleate
             • Drug Administration Schedule • Drug Interactions
             • Drug Synergism • Excitatory Amino Acid
             Antagonists • Female • Neural Inhibition •
             Nicotine • Nicotinic Agonists • Protein Subunits
             • Rats • Rats, Sprague-Dawley • Receptors,
             N-Methyl-D-Aspartate • Receptors, Nicotinic •
             Startle Reaction • drug effects • drug effects*
             • metabolism • pharmacology • pharmacology*
             • physiology},
   Abstract = {Chronic nicotine administration has long been known to
             increase the number of high-affinity alpha4beta2 nicotinic
             receptors with lesser effects on low-affinity alpha7
             nicotinic receptors. Nicotine has been shown to promote the
             release of a variety of neurotransmitters including
             glutamate. Nicotine may also interact directly with the
             glutamatergic receptors. Nicotinic-glutamate interactions
             may be critical to the long-term effects of nicotine.
             Conversely, glutamatergic drugs may interact with the
             nicotinic system. Such interactions have important
             implications in interpretation of the mechanism of drug
             actions, especially when the drugs are given together. The
             current study examined the effects of chronic administration
             of nicotine (5 mg of the nicotine base/kg/day for 28 days),
             dizocilpine (MK-801) (0.3 mg/kg/day for 28 days), an NMDA
             receptor antagonist, as well as the combination of the two
             drugs on nicotinic and NMDA receptor densities in discrete
             brain regions. The chronic dose of dizocilpine used was
             behaviorally active causing a dramatic reduction in prepulse
             inhibition (PPI) of acoustic startle response. The nicotine
             dose used did not significantly affect PPI but previously we
             have found it to be behaviorally active in improving working
             memory function. High-affinity nicotinic receptor binding,
             as has been seen previously, was significantly increased by
             chronic nicotine in most areas. Chronic dizocilpine alone
             did not affect high-affinity nicotinic receptor binding, but
             it did modify the effects of chronic nicotine, attenuating
             nicotine-induced increases in the frontal cortex and
             striatum. Low-affinity nicotinic binding was significantly
             increased by chronic nicotine in only one area, the
             cerebellum. Chronic dizocilpine significantly increased
             low-affinity nicotinic binding in several brain areas, the
             colliculi, hippocampus, and the hypothalamus. The
             combination of nicotine and dizocilpine attenuated the
             effects of each with diminished nicotine-induced increased
             nicotinic low-affinity binding in the cerebellum and
             diminished dizocilpine-induced increased nicotinic
             low-affinity binding in the hippocampus and hypothalamus. In
             contrast, chronic nicotine and dizocilpine had a mutually
             potentiating effect of increasing nicotinic low-affinity
             binding in the frontal cortex. NMDA receptor binding was
             affected only in the hippocampus, where both dizocilpine and
             nicotine significantly increased binding. Chronic nicotine
             effects on receptor regulation are significantly affected by
             concurrent blockade of NMDA glutamate receptors.},
   Language = {eng},
   Doi = {10.1016/j.brainres.2005.01.104},
   Key = {fds274514}
}

@article{fds274364,
   Author = {Levin, ED},
   Title = {Extracellular superoxide dismutase (EC-SOD) quenches free
             radicals and attenuates age-related cognitive decline:
             opportunities for novel drug development in
             aging.},
   Journal = {Current Alzheimer Research},
   Volume = {2},
   Number = {2},
   Pages = {191-196},
   Year = {2005},
   Month = {April},
   ISSN = {1567-2050},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/15974918},
   Keywords = {Aging • Animals • Cognition Disorders • Free
             Radicals • Humans • Maze Learning •
             Superoxide Dismutase • Technology, Pharmaceutical
             • biosynthesis* • drug effects • genetics
             • metabolism* • methods* • physiology •
             prevention & control • trends},
   Abstract = {Superoxide dismutase (SOD) is one of the most effective
             mechanisms in physiology for inactivating reactive oxygen
             species. Elevated SOD activity can be therapeutically useful
             by protecting against oxidative stress-induced
             neurotoxicity. Acutely increased extracellular-SOD (EC-SOD)
             activity protects against neurobehavioral impairment caused
             by acute ischemia. Chronically increased EC-SOD activity may
             also be therapeutically useful by protecting against chronic
             oxidative stress-induced neurobehavioral damage that
             accumulates during the aging process. We have found that
             mice with genetic overexpression of EC-SOD do not show the
             aging-induced decline in learning and memory that control,
             wild type mice show. From 14-22 months of age, the EC-SOD
             overexpressing mice have significantly better spatial
             learning working memory function than that of controls. This
             effect is specific to the aging period. Young adult EC-SOD
             overexpressing mice do not have better learning and memory
             function than controls. The beneficial effects of increased
             EC-SOD activity with aging may be achieved without risk of
             impairment during younger ages by chronically administering
             EC-SOD mimetics from mature adulthood into the aging period.
             Novel EC-SOD mimetics may be useful in attenuating
             aging-induced cognitive impairments and other aspects of
             physiological decline with aging.},
   Doi = {10.2174/1567205053585710},
   Key = {fds274364}
}

@article{fds136573,
   Title = {Levin ED. Marine and freshwater toxin impacts on
             neurobehavioral function. Neurotoxicol Teratol. 2005 Jul
             27.},
   Year = {2005},
   Key = {fds136573}
}

@article{fds274352,
   Author = {Levin, ED and Swain, HA and Donerly, S and Linney,
             E},
   Title = {Developmental chlorpyrifos effects on hatchling zebrafish
             swimming behavior.},
   Journal = {Neurotoxicology and Teratology},
   Volume = {26},
   Number = {6},
   Pages = {719-723},
   Year = {2004},
   Month = {November},
   ISSN = {0892-0362},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/15451035},
   Keywords = {Animals • Behavior, Animal • Chlorpyrifos •
             Cholinesterase Inhibitors • Disease Models, Animal
             • Dose-Response Relationship, Drug • Embryo,
             Nonmammalian • Habituation, Psychophysiologic •
             Larva • Motor Activity • Physical Stimulation
             • Reaction Time • Swimming • Zebrafish •
             drug effects • drug effects* • embryology •
             growth & development • methods • physiology •
             physiology* • toxicity • toxicity*},
   Abstract = {Chlorpyrifos (CPF), a widely used organophosphate
             insecticide and potent acetylcholinesterase inhibitor,
             interferes with neurobehavioral development. Rat models have
             been key in demonstrating that developmental CPF exposure
             causes learning deficits and locomotor activity alterations,
             which persist into adulthood. Complementary nonmammalian
             models can be useful in determining the neurodevelopmental
             mechanisms underlying these persisting behavioral effects.
             Zebrafish (Danio rerio) with their clear chorion and
             extensive developmental information base provide an
             excellent model for assessment of molecular processes of
             toxicant-impacted neurodevelopment. We have developed
             methods for assessing spatial discrimination learning in
             adult zebrafish and have documented persisting effects of
             developmental CPF exposure on swimming activity and learning
             after low and high doses of CPF (10 and 100 ng/ml)
             administered to zebrafish embryos on Days 1-5
             postfertilization (pf). In the current study, we developed
             methods for behavioral assessment of CPF exposure on
             swimming activity in newly hatched zebrafish. An equal area
             segmented annular grid (concentric circles divided into
             quadrants through the diameter) was made in a 16-mm diameter
             cylinder. The test area was placed on a heating device
             secured to an Olympus SZH10 dissecting scope stage.
             Zebrafish embryos were exposed to 10 ng/ml CPF, 100 ng/ml
             CPF, or vehicle control (25 microl/ml DMSO)
             (n=8-10/treatment group). Each treatment group was kept in a
             total volume of 25 ml of egg water (60 mg/ml Instant Ocean)
             including DMSO with or without CPF mixed to above dilutions
             in an incubator set at 28.5 degrees C. CPF dilutions or
             vehicle were changed daily with exposure ending on Day 5 pf.
             Testing of larval zebrafish was performed on Days 6 and 9
             pf. The fish were placed in the test cylinder with 1.5 ml of
             egg H(2)O (28.5 degrees C). After a 2-min acclimation
             period, the swimming activity of the fish was measured for a
             3-min testing session. The 100 ng/ml CPF dose caused
             significant slowing of swimming activity on Days 6 and 9 pf
             and had persisting effects of impairing spatial
             discrimination and decreasing response latency in adulthood.
             Developmental exposure to 10 ng/ml of CPF did not cause a
             significant change in locomotor activity during the period
             soon after hatching. CPF exposure during early development
             caused clear behavioral impairments detectable during the
             posthatching period. In a previous study, we found that
             early developmental CPF exposure caused behavioral
             alterations in zebrafish, which lasted throughout adulthood.
             The molecular mechanisms by which early developmental CPF
             exposure produces these behavioral impairments expressed in
             adulthood can now be studied in the zebrafish
             model.},
   Language = {eng},
   Doi = {10.1016/j.ntt.2004.06.013},
   Key = {fds274352}
}

@article{fds274390,
   Author = {Scalzo, FM and Levin, ED},
   Title = {The use of zebrafish (Danio rerio) as a model system in
             neurobehavioral toxicology.},
   Journal = {Neurotoxicology and Teratology},
   Volume = {26},
   Number = {6},
   Pages = {707-708},
   Year = {2004},
   Month = {November},
   ISSN = {0892-0362},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/15451033},
   Keywords = {Animals • Behavior, Animal • Central Nervous
             System • Disease Models, Animal* • Neurotoxins
             • Toxicology • Zebrafish • drug effects
             • drug effects* • genetics • growth &
             development • growth & development* • physiology
             • standards* • toxicity •
             trends},
   Doi = {10.1016/j.ntt.2004.06.008},
   Key = {fds274390}
}

@article{fds274425,
   Author = {Levin, ED and Chen, E},
   Title = {Nicotinic involvement in memory function in
             zebrafish.},
   Journal = {Neurotoxicology and Teratology},
   Volume = {26},
   Number = {6},
   Pages = {731-735},
   Year = {2004},
   Month = {November},
   ISSN = {0892-0362},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/15451037},
   Keywords = {Acetylcholine • Animals • Brain •
             Dose-Response Relationship, Drug • Memory • Memory
             Disorders • Models, Animal • Nicotine •
             Nicotinic Agonists • Receptors, Nicotinic •
             Spatial Behavior • Zebrafish • chemically induced*
             • drug effects • drug effects* • metabolism
             • pharmacology • pharmacology* • physiology
             • physiology* • physiopathology},
   Abstract = {Zebrafish are an emerging model for the study of the
             molecular mechanisms of brain function. To conduct studies
             of the neural bases of behavior in zebrafish, we must
             understand the behavioral function of zebrafish and how it
             is altered by perturbations of brain function. This study
             determined nicotine actions on memory function in zebrafish.
             With the methods that we have developed to assess memory in
             zebrafish using delayed spatial alternation (DSA), we
             determined the dose effect function of acute nicotine on
             memory function in zebrafish. As in rodents and primates,
             low nicotine doses improve memory in zebrafish, while high
             nicotine doses have diminished effect and can impair memory.
             This study shows that nicotine affects memory function in
             zebrafish much like in rats, mice, monkeys and humans. Now,
             zebrafish can be used to help understand the molecular
             mechanisms crucial to nicotine effects on
             memory.},
   Language = {eng},
   Doi = {10.1016/j.ntt.2004.06.010},
   Key = {fds274425}
}

@article{fds274399,
   Author = {Levin, ED and Weber, E and Icenogle, L},
   Title = {Baclofen interactions with nicotine in rats: effects on
             memory.},
   Journal = {Pharmacology, Biochemistry, and Behavior},
   Volume = {79},
   Number = {2},
   Pages = {343-348},
   Year = {2004},
   Month = {October},
   ISSN = {0091-3057},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/15501311},
   Keywords = {Animals • Baclofen • Dose-Response Relationship,
             Drug • Drug Interactions • Female • GABA
             Agonists • Maze Learning • Memory • Nicotine
             • Rats • Rats, Sprague-Dawley •
             administration & dosage* • drug effects • drug
             effects*},
   Abstract = {Nicotine has been shown in numerous previous studies to
             significantly improve memory on the radial-arm maze, yet the
             critical mechanisms underlying this effect are not fully
             characterized. Nicotine stimulates the release of a number
             of neurotransmitters important for memory function including
             (gamma-aminobutyric acid) GABA. The importance of
             nicotinic-GABA interactions regarding memory is currently
             unknown. The purpose of the current study was to determine
             the interactive effects of nicotine and the GABA agonist
             baclofen on working memory function as measured by choice
             accuracy in the radial-arm maze. Female Sprague-Dawley rats
             trained to asymptotic performance levels on a win-shift
             eight-arm radial maze task were used for assessment of
             nicotine-baclofen interactions. Low doses of baclofen
             improved memory performance while higher doses impaired it.
             Nicotine, as seen before, improved memory performance.
             Nicotine also significantly reversed the higher dose
             baclofen-induced deficit. These data show the importance of
             both nicotinic and GABA systems in working memory function
             and the interactions between these two transmitter receptor
             systems. This not only provides information concerning the
             neural bases of cognitive performance, it also lends insight
             into new combination treatments for memory
             impairment.},
   Doi = {10.1016/j.pbb.2004.08.013},
   Key = {fds274399}
}

@article{fds274505,
   Author = {Rezvani, AH and Levin, ED},
   Title = {Adolescent and adult rats respond differently to nicotine
             and alcohol: motor activity and body temperature.},
   Journal = {International Journal of Developmental Neuroscience : the
             Official Journal of the International Society for
             Developmental Neuroscience},
   Volume = {22},
   Number = {5-6},
   Pages = {349-354},
   Year = {2004},
   Month = {August},
   ISSN = {0736-5748},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/15380834},
   Keywords = {Adaptation, Physiological • Age Factors • Aging
             • Animals • Animals, Newborn • Dose-Response
             Relationship, Drug • Drug Interactions • Ethanol
             • Female • Injections, Intraperitoneal •
             Injections, Subcutaneous • Locomotion • Nicotine
             • Rats • Rats, Sprague-Dawley • Sex Factors
             • administration & dosage* • drug effects •
             drug effects* • physiology • physiology*},
   Abstract = {Alcohol and nicotine are the most widely abused drugs in the
             world. The use of these addictive drugs often begins in
             adolescence, however, little is known about the different
             impacts of nicotine and alcohol on adolescents versus
             adults. This study examined both the individual and combined
             effects of nicotine and alcohol on body temperature and
             locomotor activity in adolescent and adults rats. Rats were
             injected with saline (SC) + saline (IP), nicotine (SC) +
             saline (IP), alcohol (IP) + saline (SC) or alcohol (IP) +
             nicotine (SC). The dose selected for nicotine was 0.2 mg/kg
             and for alcohol 2.5 g/kg (16% v/v). For each age/treatment,
             10-13 animals were used, with each animal receiving only one
             treatment. In regards to body temperature, both nicotine and
             alcohol caused a significant age x drug interaction. The
             combination of nicotine and alcohol caused greater drop in
             body temperature in adolescent than in adult rats. Neither
             of the two drugs, when given alone, caused differential
             effects in adolescents or adult rats, though both resulted
             in drop in body temperature. In terms of locomotor activity,
             the treatment that produced a significantly different effect
             between adolescents and adults was nicotine alone. Nicotine
             significantly decreased locomotor activity in adolescent
             compared to adult rats. These preliminary results suggest
             that adolescent rats may have an increased sensitivity to
             nicotine and alcohol, which may consequently impact their
             initial addiction to these two drugs.},
   Doi = {10.1016/j.ijdevneu.2004.03.007},
   Key = {fds274505}
}

@article{fds274217,
   Author = {Rezvani, AH and Levin, ED},
   Title = {Erratum: Nicotine-antipsychotic drug interactions and
             attentional performance in female rats (European Journal of
             Pharmacology (2004) 486 (175-182) DOI: 10.1016/j.ejphar.2003.12.021.)},
   Journal = {European Journal of Pharmacology},
   Volume = {489},
   Number = {3},
   Pages = {215},
   Publisher = {Elsevier BV},
   Year = {2004},
   Month = {April},
   url = {http://dx.doi.org/10.1016/j.ejphar.2004.03.009},
   Doi = {10.1016/j.ejphar.2004.03.009},
   Key = {fds274217}
}

@article{fds316094,
   Author = {Rezvani, AH and Levin, ED},
   Title = {Nicotine-antipsychotic drug interactions and attentional
             performance in female rats (vol 486, pg 175,
             2004)},
   Journal = {European Journal of Pharmacology},
   Volume = {489},
   Number = {3},
   Pages = {215-215},
   Publisher = {Elsevier},
   Year = {2004},
   Month = {April},
   ISSN = {0014-2999},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000220892500011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Doi = {10.1016/j.ejphar.2004.03.009},
   Key = {fds316094}
}

@article{fds274395,
   Author = {Rezvani, AH and Levin, ED},
   Title = {Nicotine-antipsychotic drug interactions and attentional
             performance in female rats.},
   Journal = {European Journal of Pharmacology},
   Volume = {486},
   Number = {2},
   Pages = {175-182},
   Year = {2004},
   Month = {February},
   ISSN = {0014-2999},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/14975706},
   Keywords = {Animals • Antipsychotic Agents • Attention •
             Central Nervous System Stimulants • Clozapine •
             Dose-Response Relationship, Drug • Drug Interactions
             • Female • Haloperidol • Nicotine •
             Photic Stimulation • Psychomotor Performance •
             Rats • Rats, Sprague-Dawley • Risperidone •
             administration & dosage • drug effects* •
             pharmacokinetics • pharmacology • pharmacology*
             • physiology},
   Abstract = {Schizophrenia is marked by pronounced cognitive impairments
             in addition to the hallmark psychotic symptoms like
             hallucinations. Antipsychotic drugs can effectively reduce
             these hallucinations; however, the drugs have not resolved
             the cognitive impairment. Interestingly, nicotine, a drug
             commonly self-administered by people with schizophrenia, has
             been shown to significantly improve cognitive function of
             people with schizophrenia. The current study was conducted
             to determine the effect of typical (haloperidol) and
             atypical (clozapine and risperidone) antipsychotic drug
             treatment on sustained attention in rats performing a visual
             signal detection task. In addition, the interaction of
             haloperidol with chronic nicotine administration was
             assessed. Female Sprague-Dawley rats were injected
             subcutaneously with clozapine (0, 0.6, 1.25 and 2.5 mg/kg),
             risperidone (0, 0.025, 0.05 and 0.1 mg/kg) or haloperidol
             (0, 0.01, 0.02 and 0.04 mg/kg). In the second part of the
             study, the interaction of acute haloperidol (0, 0.005, 0.01
             and 0.02 mg/kg) and chronic nicotine (5 mg/kg/day, for 4
             weeks via osmotic minipump) was characterized. Clozapine,
             risperidone and haloperidol all caused dose-related
             impairments in percent hit performance. There was a
             significant linear dose-related impairment in percent hit
             caused by risperidone. All the doses of clozapine caused a
             significant impairment in percent hit at the higher
             luminance intensities in the visual signal detection task.
             The 0.01 and 0.02 mg/kg haloperidol doses caused significant
             decreases in percent hit. The 0.04 mg/kg haloperidol dose
             impaired performance of the task to the point that reliable
             choice accuracy measurements could not be made. Chronic
             nicotine infusion significantly diminished the impairing
             effects of haloperidol on performance during weeks 1-2. In
             summary, both typical and atypical antipsychotic drugs
             significantly impaired sustained attention in rats.
             Haloperidol was more detrimental than clozapine and
             risperidone. Chronic nicotine diminished the adverse effects
             of haloperidol on performance. This study establishes a
             paradigm to reliably determine the attentional impairment
             caused by antipsychotic drugs.},
   Language = {eng},
   Doi = {10.1016/j.ejphar.2003.12.021},
   Key = {fds274395}
}

@article{fds274370,
   Author = {White, HK and Levin, ED},
   Title = {Chronic transdermal nicotine patch treatment effects on
             cognitive performance in age-associated memory
             impairment.},
   Journal = {Psychopharmacology},
   Volume = {171},
   Number = {4},
   Pages = {465-471},
   Year = {2004},
   Month = {February},
   ISSN = {0033-3158},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/14534771},
   Keywords = {Administration, Cutaneous • Aged • Aged, 80 and
             over • Aging • Cognition • Cross-Over Studies
             • Double-Blind Method • Drug Administration
             Schedule • Female • Humans • Male •
             Memory Disorders • Middle Aged • Nicotine •
             Psychomotor Performance • Reaction Time •
             administration & dosage* • drug effects* • drug
             therapy* • physiology • psychology •
             psychology*},
   Abstract = {OBJECTIVES: Chronic transdermal nicotine has been found to
             improve attentional performance in patients with Alzheimer's
             disease (AD), but little is known about chronic nicotine
             effects in age-associated memory impairment (AAMI), a milder
             form of cognitive dysfunction. The current study was
             performed to determine the clinical and neuropsychological
             effects of chronic transdermal nicotine in AAMI subjects
             over a 4-week period. DESIGN: The double-blind,
             placebo-controlled, cross-over study consisted of two 4-week
             periods separated by a 2-week washout period. SETTING: An
             outpatient setting was used. PARTICIPANTS: The subjects (
             n=11) met criteria for AAMI. INTERVENTIONS: The subjects
             were given nicotine patches (Nicotrol) to wear for 16 h a
             day at the following doses: 5 mg/day during week 1, 10
             mg/day during week 2 and week 3 and 5 mg/day during week 4.
             MEASUREMENTS: The effects of nicotine treatment were
             determined with the clinical global impressions
             questionnaire, Conners' Continuous Performance test, and the
             automated neuropsychologic assessment metrics (ANAM)
             computerized neuropsychology battery. RESULTS: Nicotine
             significantly improved the clinical global impression score
             as assessed by participants, as well as objective tests of
             attentional function on the Connors' Continuous Performance
             Test and decision reaction time on the neuropsychology test
             battery. Nicotine did not improve performance on other tests
             measuring motor and memory function. CONCLUSION: Chronic
             transdermal nicotine treatment in AAMI subjects caused a
             sustained improvement in clinical symptoms and objective
             computerized tests of attention. These results support the
             further investigation of nicotinic treatment as a promising
             therapy for AAMI.},
   Language = {eng},
   Doi = {10.1007/s00213-003-1614-8},
   Key = {fds274370}
}

@article{fds274388,
   Author = {Levin, ED and Brunssen, S and Wolfe, GW and Harry,
             GJ},
   Title = {Neurobehavioral assessment of mice after developmental AZT
             exposure.},
   Journal = {Neurotoxicology and Teratology},
   Volume = {26},
   Number = {1},
   Pages = {65-71},
   Year = {2004},
   Month = {January},
   ISSN = {0892-0362},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/15001215},
   Keywords = {Age Factors • Animals • Animals, Newborn •
             Anti-HIV Agents • Dose-Response Relationship, Drug
             • Eating • Female • Male • Maze Learning
             • Mice • Motor Activity • Pregnancy •
             Prenatal Exposure Delayed Effects* • Psychomotor
             Performance • Reaction Time • Retention
             (Psychology) • Sex Factors • Survival • Time
             Factors • Zidovudine • drug effects • drug
             effects* • toxicity • toxicity*},
   Abstract = {Azidothymidine (AZT) is administered to pregnant women with
             HIV to prevent the spread of infection to their fetuses.
             Since gestation is a period of critical neurodevelopment, it
             is important to determine the risk AZT exposure may pose to
             neurobehavioral function of the offspring. The current study
             focused on teratological risks of developmental AZT exposure
             to neurocognitive function. Male and female Swiss mice were
             administered AZT or vehicle (0, 100, or 200 mg/kg/day po
             given twice daily in equal amounts for 32 weeks before and
             during gestation). Adult male and female offspring (n =
             10/sex/treatment group) underwent neurobehavioral testing
             focused on determining learning and memory capabilities in
             the radial-arm maze. AZT exposure did not cause significant
             deficits during radial-arm maze acquisition. No impairment
             was seen in asymptotic levels of choice accuracy indicative
             of working memory function. Attempts to unmask subtle
             learning impairments following developmental AZT by the
             introduction of behavioral challenges such as reduction of
             motivational state (food restriction either 4-6 h or 22-24
             h) or imposition of intrasession delays of 1.5 min to 2.5 h
             were unsuccessful. With a 4-week intersession delay, a
             significant AZT Treatment x Delay effect was seen with a
             significantly greater decline seen in the controls as
             compared to the 100 mg/kg/day AZT group. Locomotor activity
             on the radial-arm maze was significantly affected by AZT
             treatment (100 mg/kg/day) during the acquisition phase, but
             not during the other test phases. No behavioral alterations
             were seen related to stress as measured by the elevated plus
             maze. Vestibulomotor functioning on the balance beam
             remained unaltered. Using an extended dosing regimen
             including dosing of both sires and dams, as well as placing
             a greater demand on reproductive system performance with
             three continuous breedings, this study detected only subtle
             neurobehavioral impairments in mice after prenatal AZT
             exposure at clinically relevant doses.},
   Doi = {10.1016/j.ntt.2003.10.001},
   Key = {fds274388}
}

@article{fds274486,
   Author = {Icenogle, LM and Christopher, NC and Blackwelder, WP and Caldwell,
             DP and Qiao, D and Seidler, FJ and Slotkin, TA and Levin,
             ED},
   Title = {Behavioral alterations in adolescent and adult rats caused
             by a brief subtoxic exposure to chlorpyrifos during
             neurulation.},
   Journal = {Neurotoxicology and Teratology},
   Volume = {26},
   Number = {1},
   Pages = {95-101},
   Year = {2004},
   Month = {January},
   ISSN = {0892-0362},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/15001218},
   Keywords = {Animals • Animals, Newborn • Behavior, Animal
             • Behavioral Symptoms • Brain • Chlorpyrifos
             • Dose-Response Relationship, Drug • Drug
             Interactions • Female • Habituation,
             Psychophysiologic • Inhibition (Psychology) •
             Insecticides • Maze Learning • Memory, Short-Term
             • Motor Activity • Muscarinic Antagonists •
             Pregnancy • Prenatal Exposure Delayed Effects* •
             Rats • Reaction Time • Scopolamine Hydrobromide
             • chemically induced* • drug effects • drug
             effects* • embryology • growth & development
             • pharmacology • physiopathology •
             toxicity*},
   Abstract = {The widely used organophosphate insecticide, chlorpyrifos
             (CPF), elicits neurobehavioral abnormalities after
             apparently subtoxic neonatal exposures. In the current
             study, we administered 1 or 5 mg/kg/day of CPF to pregnant
             rats on gestational days 9-12, the embryonic phase spanning
             formation and closure of the neural tube. Although there
             were no effects on growth or viability, offspring showed
             behavioral abnormalities when tested in adolescence and
             adulthood. In the CPF-exposed groups, locomotor
             hyperactivity was noted in early T-maze trials, and in the
             elevated plus-maze; alterations in the rate of habituation
             were also identified. Learning and memory were adversely
             affected, as assessed using the 16-arm radial maze. Although
             all CPF-exposed animals eventually learned the task,
             reference and working memory were impaired in the early
             training sessions. After training, rats in the CPF group did
             not show the characteristic amnestic effect of scopolamine,
             a muscarinic acetylcholine antagonist, suggesting that,
             unlike the situation in the control group, muscarinic
             pathways were not used to solve the maze. These results
             indicate that apparently subtoxic CPF exposure during
             neurulation adversely affects brain development, leading to
             behavioral anomalies that selectively include impairment of
             cholinergic circuits used in learning and memory. The
             resemblance of these findings to those of late gestational
             or neonatal CPF exposure indicates a prolonged window of
             vulnerability of brain development to CPF.},
   Language = {eng},
   Doi = {10.1016/j.ntt.2003.09.001},
   Key = {fds274486}
}

@article{fds274393,
   Author = {Aldridge, JE and Gibbons, JA and Flaherty, MM and Kreider, ML and Romano, JA and Levin, ED},
   Title = {Heterogeneity of toxicant response: sources of human
             variability.},
   Journal = {Toxicological Sciences},
   Volume = {76},
   Number = {1},
   Pages = {3-20},
   Year = {2003},
   Month = {November},
   ISSN = {1096-6080},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/12883075},
   Keywords = {Age Factors • Cytochrome P-450 Enzyme System •
             Drug Toxicity* • Environmental Pollutants •
             Genetic Predisposition to Disease* • Humans • Risk
             Assessment • Sex Factors • adverse effects* •
             etiology • genetics • genetics* •
             metabolism},
   Abstract = {While risk assessment models attempt to predict human risk
             to toxicant exposure, in many cases these models cannot
             account for the wide variety of human responses. This review
             addresses several primary sources of heterogeneity that may
             affect individual responses to drug or toxicant exposure.
             Consideration was given to genetic polymorphisms,
             age-related factors during development and senescence,
             gender differences associated with hormonal function, and
             preexisting diseases influenced by toxicant exposure. These
             selected examples demonstrate the need for additional steps
             in risk assessment that are needed to more accurately
             predict human responses to toxicants and
             drugs.},
   Doi = {10.1093/toxsci/kfg204},
   Key = {fds274393}
}

@article{fds274404,
   Author = {Levin, ED and Sledge, D and Baruah, A and Addy, NA},
   Title = {Ventral hippocampal NMDA blockade and nicotinic effects on
             memory function.},
   Journal = {Brain Research Bulletin},
   Volume = {61},
   Number = {5},
   Pages = {489-495},
   Year = {2003},
   Month = {September},
   ISSN = {0361-9230},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/13679247},
   Keywords = {Animals • Dizocilpine Maleate • Drug Interactions
             • Excitatory Amino Acid Antagonists • Female
             • Hippocampus • Maze Learning • Memory •
             Memory Disorders • Neural Pathways • Neurons
             • Nicotine • Rats • Rats, Sprague-Dawley
             • Reaction Time • Receptors, N-Methyl-D-Aspartate
             • Receptors, Nicotinic • Synaptic Transmission
             • chemically induced • cytology • drug
             effects • drug effects* • metabolism •
             pharmacology • physiology • physiopathology},
   Abstract = {Nicotinic acetylcholine and NMDA glutamate receptors play
             critical roles in memory function. The brain areas involved
             in their interaction are still under investigation. One
             likely area is the hippocampus. Ventral hippocampal
             administration of nicotinic antagonists impair memory.
             Hippocampal administration of NMDA antagonists also cause
             memory impairments. We evaluated the importance of ventral
             hippocampal NMDA receptors for nicotinic actions on memory
             by testing the impact of systemic nicotine on memory with
             and without administration of the NMDA antagonist
             dizocilpine into the ventral hippocampus. Sprague-Dawley
             rats (N=11) trained on the 16-arm radial maze were
             bilaterally implanted with local infusion cannulae in the
             ventral hippocampus. The effects on memory function of
             ventral hippocampal infusions of 0, 2, 6 and 18 microg per
             side of dizocilpine were examined with and without acute
             systemic nicotine administration (0 or 0.4 mg/kg). The
             dizocilpine doses tested did not cause memory deficits by
             themselves but only did so when given in combination with
             systemic nicotine. Blocking NMDA ventral hippocampal actions
             revealed an impairing action of nicotine on memory. Nicotine
             effects on other non-NMDA hippocampal receptor systems or
             extra-hippocampal systems may have been left unchecked by
             the diminished nicotinic effect on ventral hippocampal NMDA
             receptors.},
   Doi = {10.1016/s0361-9230(03)00183-7},
   Key = {fds274404}
}

@article{fds274441,
   Author = {Levin, ED and Rezvani, AH and Montoya, D and Rose, JE and Swartzwelder,
             HS},
   Title = {Adolescent-onset nicotine self-administration modeled in
             female rats.},
   Journal = {Psychopharmacology},
   Volume = {169},
   Number = {2},
   Pages = {141-149},
   Year = {2003},
   Month = {September},
   ISSN = {0033-3158},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/12764575},
   Keywords = {Adolescent • Age Factors • Age of Onset* •
             Animals • Disease Models, Animal • Dose-Response
             Relationship, Drug • Female • Humans •
             Hypothermia • Infusions, Intravenous • Injections,
             Subcutaneous • Motor Activity • Nicotine •
             Rats • Rats, Sprague-Dawley • Self Administration*
             • Time Factors • administration & dosage* •
             adverse effects • chemically induced • drug
             effects • pharmacokinetics* • physiology*},
   Abstract = {RATIONALE: Although the great majority of tobacco addiction
             begins during adolescence, little is known about
             differential nicotine effects in adolescents versus adults.
             OBJECTIVES: A rat model was used to determine the impact of
             the age of onset on nicotine self-administration. METHODS:
             In expt 1, nicotine self-administration of female
             Sprague-Dawley rats over a range of acute doses (0.01-0.08
             mg/kg per infusion) was determined in adolescent (beginning
             at 54-62 days) versus adult (beginning at 84-90 days). In
             expt 2, chronic nicotine self-administration over 4 weeks
             from adolescence into adulthood was compared with the
             chronic self-administration beginning in adulthood. In expt
             3, adolescent-adult differences in nicotine effects on body
             temperature and locomotor responses were determined.
             RESULTS: Adolescent-onset rats showed a significant main
             effect of increased nicotine intake compared with
             adult-onset rats in an eight-fold range of acute unit
             doses/infusion. Significant age differences were also seen
             in the chronic level of nicotine self-administration. Over 4
             weeks, the adolescent-onset group had nearly double the rate
             of nicotine self-administration of the benchmark nicotine
             dose (0.03 mg/kg per infusion) compared to the adult-onset
             group. This increased nicotine intake persisted into
             adulthood. Adolescent rats had significantly greater
             response than adults to the hypothermic effects of nicotine,
             but had significantly less response than adults to the
             reduction in locomotor activity seen after nicotine.
             CONCLUSIONS: Adolescent-onset nicotine self-administration
             in female rats was associated with significantly higher
             levels of nicotine self-administration versus rats, which
             began nicotine self-administration in adulthood. This
             greater self-administration persists into adulthood and may
             underlie greater propensity of adolescents to nicotine
             addiction.},
   Doi = {10.1007/s00213-003-1486-y},
   Key = {fds274441}
}

@article{fds274397,
   Author = {Rezvani, AH and Levin, ED},
   Title = {Nicotine-alcohol interactions and attentional performance on
             an operant visual signal detection task in female
             rats.},
   Journal = {Pharmacology, Biochemistry, and Behavior},
   Volume = {76},
   Number = {1},
   Pages = {75-83},
   Year = {2003},
   Month = {August},
   ISSN = {0091-3057},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/13679219},
   Keywords = {Animals • Attention • Conditioning, Operant •
             Dose-Response Relationship, Drug • Drug Interactions
             • Ethanol • Female • Nicotine • Photic
             Stimulation • Psychomotor Performance • Rats
             • Rats, Sprague-Dawley • antagonists & inhibitors
             • drug effects* • methods • pharmacology*
             • physiology},
   Abstract = {Nicotine and alcohol are very often co-used and co-abused.
             Thus, it is important to understand their interactions. In
             many ways, nicotine and alcohol have opposing effects. This
             can be clearly seen in terms of their effects on cognitive
             function. Nicotine effectively improves attention while
             alcohol impairs it. The current study was conducted to
             determine in a rat model the interaction of nicotine and
             alcohol on attention using an operant visual signal
             detection task. It is hypothesized that nicotine would
             reverse the alcohol-induced impairment in accuracy of
             performance in this task. Female Sprague-Dawley rats (N=35)
             were trained on a visual operant signal detection task for
             food reinforcement with 300 trials/session in three equal
             time blocks. The rats were divided into poor and good
             performers according to their predrug baseline performance
             accuracy. The first experiment examined the dose-effect
             function of alcohol (0, 0.375, and 0.75 g/kg i.p.) on this
             task. The lower alcohol dose significantly impaired percent
             correct rejection in the high-performing rats but not the
             low-performing rats. The higher alcohol dose significantly
             impaired percent hit performance during the first two thirds
             of the session in both high- and low-performing groups. The
             second experiment examined alcohol (0.75 g/kg i.p.)
             interactions with nicotine (0, 12.5, 25, and 50 microg/kg
             s.c.) on attentional performance. The 25 and 50 microg/kg
             nicotine doses caused a significant (P<.05) improvement in
             hit accuracy. Alcohol blocked this nicotine-induced
             improvement, even though at this later time it no longer had
             an effect of its own. In the high baseline group, the 25
             microg/kg nicotine dose also caused a significant (P<.025)
             improvement in hit accuracy. As in Experiment 1, the high
             baseline group was not significantly impaired by 0.75 g/kg
             of alcohol. However, this alcohol dose did eliminate the
             nicotine-induced improvement. These results suggest that
             alcohol, when given alone, impairs sustained attention and
             blocks nicotine-induced attentional improvements even when
             it does not cause impairments on its own.},
   Doi = {10.1016/s0091-3057(03)00193-x},
   Key = {fds274397}
}

@article{fds274469,
   Author = {Levin, ED and Christopher, CN},
   Title = {Lobeline-induced learning improvement of rats in the
             radial-arm maze.},
   Journal = {Pharmacology, Biochemistry, and Behavior},
   Volume = {76},
   Number = {1},
   Pages = {133-139},
   Year = {2003},
   Month = {August},
   ISSN = {0091-3057},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/13679226},
   Keywords = {Animals • Dose-Response Relationship, Drug •
             Female • Lobeline • Maze Learning • Rats
             • Rats, Sprague-Dawley • drug effects* •
             pharmacology* • physiology},
   Abstract = {Lobeline is a nicotinic ligand with some nicotine-like
             effects, but with some atypical effects as well, including
             actions as a nicotinic antagonist. Lobeline, like nicotine,
             has been found to significantly improve memory function as
             well as provide anxiolytic-like effects in the elevated plus
             maze. Lobeline effects on learning remain to be fully
             characterized. Nicotine has been found to improve learning
             of shock avoidance tasks. Other nicotinic agonists also have
             been shown to improve learning performance. However, this
             effect is limited. In some tasks, nicotine has been found to
             cause deficits. In the current study, effects of lobeline
             and nicotine injections were assessed in a repeated
             acquisition procedure in the radial-arm maze for 3 weeks of
             drug administration. Lobeline (0.3 and 0.9 mg/kg) improved
             learning on the radial-arm maze. Neither nicotine dose (0.1
             and 0.3 mg/kg) improved learning. This nicotine dose range
             was previously found to improve post-acquisition working
             memory performance in the radial-arm maze. The atypical
             effects of lobeline may underlie its greater efficacy than
             nicotine for improving repeated acquisition. The effect of
             lobeline improving learning may be useful in the development
             of novel treatments for learning deficits.},
   Doi = {10.1016/s0091-3057(03)00216-8},
   Key = {fds274469}
}

@article{fds274350,
   Author = {Levin, ED and Blackwelder, WP and Glasgow, HB and Burkholder, JM and Moeller, PDR and Ramsdell, JS},
   Title = {Learning impairment caused by a toxin produced by Pfiesteria
             piscicida infused into the hippocampus of
             rats.},
   Journal = {Neurotoxicology and Teratology},
   Volume = {25},
   Number = {4},
   Pages = {419-426},
   Year = {2003},
   Month = {July},
   ISSN = {0892-0362},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/12798959},
   Keywords = {Animals • Behavior, Animal • Female •
             Hippocampus • Learning Disorders • Maze Learning
             • Neurotoxins • Pfiesteria piscicida •
             Protozoan Infections, Animal • Rats • Rats,
             Sprague-Dawley • Reaction Time • Time Factors
             • drug effects • etiology* • metabolism*
             • microbiology* • physiopathology* •
             toxicity*},
   Abstract = {Pfiesteria piscicida, an estuarine dinoflagellate, which has
             been shown to kill fish, has also been associated with
             neurocognitive deficits in humans. With a rat model, we have
             demonstrated the cause-and-effect relationship between
             Pfiesteria exposure and learning impairment. In several
             studies, we have replicated the finding in Sprague-Dawley
             rats that exposure to fixed acute doses of Pfiesteria cells
             or filtrates caused radial-arm maze learning impairment.
             Recently, this finding of Pfiesteria-induced learning
             impairment in rats has been independently replicated in
             another laboratory as well. We have demonstrated significant
             Pfiesteria-induced learning impairment in both the win-shift
             and repeated-acquisition tasks in the radial-arm maze and in
             reversal learning in a visual operant signal detection task.
             These learning impairments have been seen as long as 10
             weeks after a single acute exposure to Pfiesteria. In the
             current study, we used a hydrophilic toxin isolated from
             clonal P. piscicida cultures (PfTx) and tested its effect
             when applied locally to the ventral hippocampus on repeated
             acquisition of rats in the radial-arm maze. Toxin exposure
             impaired choice accuracy in the radial-arm maze repeated
             acquisition procedure. The PfTx-induced impairment was seen
             at the beginning of the session and the early learning
             deficit was persistent across 6 weeks of testing after a
             single administration of the toxin. Eventually, with enough
             practice, in each session, the PfTx-exposed rats did learn
             that session's problem as did control rats. This model has
             demonstrated the cause-and-effect relationship between
             exposure to a hydrophilic toxin produced by P. piscicida and
             learning impairment, and specifically that the ventral
             hippocampus was critically involved.},
   Doi = {10.1016/s0892-0362(03)00011-4},
   Key = {fds274350}
}

@article{fds274363,
   Author = {May-Simera, H and Levin, ED},
   Title = {NMDA systems in the amygdala and piriform cortex and
             nicotinic effects on memory function.},
   Journal = {Brain Research. Cognitive Brain Research},
   Volume = {17},
   Number = {2},
   Pages = {475-483},
   Year = {2003},
   Month = {July},
   ISSN = {0926-6410},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/12880917},
   Keywords = {Amygdala • Animals • Cerebral Cortex •
             Dizocilpine Maleate • Dose-Response Relationship, Drug
             • Excitatory Amino Acid Antagonists • Female
             • Memory • Nicotine • Rats • Rats,
             Sprague-Dawley • Receptors, N-Methyl-D-Aspartate •
             antagonists & inhibitors* • drug effects* •
             pharmacology • pharmacology* •
             physiology},
   Abstract = {Both nicotinic cholinergic and NMDA glutaminergic systems
             are important for memory function. Nicotine has been found
             repeatedly to significantly improve working memory
             performance in the radial-arm maze. The NMDA antagonist
             dizocilpine has been found to impair working memory
             performance. There is neuropharmacological evidence that
             these two systems are functionally related. Nicotine is
             potent at releasing many transmitters including glutamate.
             The current study was conducted to examine the interaction
             of nicotinic and NMDA systems within the amygdala with
             regard to working and reference memory. Rats were trained on
             a working/reference procedure on a 16-arm radial maze. After
             acquisition, local infusion cannulae were implanted
             bilaterally into the amygdala and piriform cortex using
             stereotaxic techniques. Then 20 min prior to running the
             rats on the radial-arm maze, they were injected
             subcutaneously with (-) nicotine ditartrate at doses of 0
             and 0.4 mg/kg. Following this, the rats received local
             infusions of (+) dizocilpine maleate (MK-801) at doses of 0,
             2, 6 and 18 microg per side into the lateral amygdala or
             piriform cortex 10 min prior to running on the radial-arm
             maze. Each of the eight nicotine and dizocilpine
             combinations was administered to each rat in a
             counterbalanced order. After completion of the drug sessions
             the rats were sacrificed, and using histological methods the
             cannulae placements were verified. Acute amygdalar infusions
             of the NMDA glutamate receptor antagonist dizocilpine
             induced dose-related working and reference memory deficits
             in the radial-arm maze. Systemic nicotine was not seen to
             reverse these effects. Dizocilpine infusions into the
             adjacent piriform cortex did not impair memory function,
             supporting the specificity of dizocilpine effects in the
             amygdala. Latency effects were seen with both drugs in both
             areas. Latencies were decreased with both systemic nicotine
             and dizocilpine in both the lateral amygdala and the
             piriform cortex. This study demonstrated the importance of
             NMDA glutamate systems in the amygdala for
             appetitively-motivated spatial memory performance.},
   Doi = {10.1016/s0926-6410(03)00163-0},
   Key = {fds274363}
}

@article{fds274368,
   Author = {Rezvani, AH and Levin, ED},
   Title = {Nicotinic-glutamatergic interactions and attentional
             performance on an operant visual signal detection task in
             female rats.},
   Journal = {European Journal of Pharmacology},
   Volume = {465},
   Number = {1-2},
   Pages = {83-90},
   Year = {2003},
   Month = {March},
   ISSN = {0014-2999},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/12650836},
   Keywords = {Animals • Attention • Behavior, Animal •
             Conditioning, Operant • Dizocilpine Maleate •
             Dose-Response Relationship, Drug • Drug Interactions
             • Excitatory Amino Acid Antagonists • Male •
             Nicotine • Nicotinic Agonists • Psychomotor
             Performance • Rats • Rats, Sprague-Dawley •
             Signal Detection (Psychology) • drug effects •
             drug effects* • pharmacology*},
   Abstract = {Nicotinic systems have been shown to be critically involved
             in cognitive function including attention. Nicotine has been
             shown to improve performance on attentional tasks in humans
             with Alzheimer's disease, schizophrenia and attention
             deficit hyperactivity disorder. Nicotine has mixed effects
             on attentional accuracy in unimpaired rats with findings of
             increased, reduced or unaltered accuracy under different
             conditions. Nicotine effects on attentional function in rats
             might be more clearly seen in reversing impaired
             performance. The current study determined nicotine effects
             on attentional accuracy reduced by the NMDA receptor
             antagonist dizocilpine (MK-801). Sprague-Dawley rats (N=35)
             were trained on a food-motivated two-lever operant task with
             one lever correct after a brief visual signal (0.027-1.22
             lx) for hits and the other lever correct after the absence
             of a signal for correct rejections. First, a dose response
             study of dizocilpine was conducted to determine the
             threshold for impairment. The rats were administered acute
             doses of dizocilpine (0, 12.5, 25 and 50 microg/kg, sc). The
             50 microg/kg dose caused significant (p<0.0005) reduction in
             percent hit at the four highest signal intensities. Percent
             correct rejection was also significantly lowered by this
             dose (p<0.005). No effect was seen with 12.5 microg/kg and
             only minimal effect seen with 25 microg/kg. Then,
             nicotine-dizocilpine interactions were investigated. The
             rats were administered acute doses of dizocilpine (0, 37.5
             and 50 microg/kg, sc) and nicotine (0, 25 and 50 microg/kg,
             sc), alone or in combination. Percent hit was affected by
             nicotine and dizocilpine in a complex fashion with only the
             nicotinexdizocilpinexsignal intensity interaction being
             significant (p<0.05). Percent correct rejection showed a
             more straightforward effect. Percent correct rejection was
             significantly reduced by 50 microg/kg dizocilpine (p<0.025).
             The addition of 25 microg/kg of nicotine significantly
             (p<0.025) reversed the dizocilpine-induced reduction of
             correct rejection. This study shows that dizocilpine reduces
             signal detection accuracy in a dose-dependent fashion.
             Nicotine can partially counteract an aspect of this
             reduction by reversing the dizocilpine-induced reduction of
             correct rejection.},
   Doi = {10.1016/s0014-2999(03)01439-0},
   Key = {fds274368}
}

@article{fds274347,
   Author = {Yang, YK and McEvoy, JP and Wilson, WH and Levin, ED and Rose,
             JE},
   Title = {Reliabilities and intercorrelations of reported and
             objective measures of smoking in patients with
             schizophrenia.},
   Journal = {Schizophrenia Research},
   Volume = {60},
   Number = {1},
   Pages = {9-12},
   Year = {2003},
   Month = {March},
   ISSN = {0920-9964},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/12505133},
   Keywords = {Adult • Antipsychotic Agents • Carbon Dioxide
             • Female • Haloperidol • Humans • Male
             • Matched-Pair Analysis • Middle Aged •
             Psychiatric Status Rating Scales • Questionnaires
             • Reproducibility of Results • Schizophrenia
             • Smoking • Statistics • Tobacco Use Disorder
             • adverse effects • complications* •
             diagnosis • drug therapy • epidemiology •
             metabolism • metabolism* • methods •
             therapeutic use},
   Abstract = {We examined the test-retest reliabilities of reported and
             objective measures of smoking, and the intercorrelations
             among these measures, in acutely psychotic patients with
             schizophrenia to determine whether severe psychiatric
             illness affects the utility of these variables. All measures
             demonstrated good test-retest reliability. Objective
             measures of smoking were consistently intercorrelated and
             should be the preferred outcome measures in studies testing
             strategies to reduce smoking.},
   Doi = {10.1016/s0920-9964(02)00208-6},
   Key = {fds274347}
}

@article{fds274461,
   Author = {Addy, NA and Nakijama, A and Levin, ED},
   Title = {Nicotinic mechanisms of memory: effects of acute local
             DHbetaE and MLA infusions in the basolateral
             amygdala.},
   Journal = {Brain Research. Cognitive Brain Research},
   Volume = {16},
   Number = {1},
   Pages = {51-57},
   Year = {2003},
   Month = {March},
   ISSN = {0926-6410},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/12589888},
   Keywords = {Aconitine • Amygdala • Animals •
             Dihydro-beta-Erythroidine • Dose-Response Relationship,
             Drug • Female • Maze Learning • Memory •
             Nicotinic Antagonists • Rats • Rats,
             Sprague-Dawley • Reaction Time • Receptors,
             Nicotinic • administration & dosage • analogs &
             derivatives* • anatomy & histology •
             classification • drug effects • drug effects*
             • pharmacology* • physiology},
   Abstract = {Nicotine has been shown to improve working memory. The
             neural mechanisms underlying this effect are still being
             determined. The ventral hippocampus is critical for
             nicotinic effects on memory. Local ventral hippocampal
             infusions of either the nicotinic alpha7 nicotinic receptor
             antagonist methyllycaconitine (MLA) or the alpha4beta2
             nicotinic receptor antagonist dihydro-beta-erythroidine
             (DHbetaE) caused working memory impairments, but no additive
             effects were seen. Other areas, such as the amygdala, also
             likely play important roles in nicotinic effects on memory.
             Amygdalar lesions cause memory impairment and there is a
             dense concentration of nicotinic receptors in the
             basolateral amygdala. The current study used local
             basolateral amygdalar infusions of the nicotinic antagonists
             MLA and DHbetaE to determine the involvement of alpha7 and
             alpha4beta2 nicotinic receptors in spatial working and
             reference memory. Rats (n=8) were trained in the 16-arm
             radial maze and were implanted with bilateral infusion
             cannulae into the basolateral amygdala. Acute infusions of
             MLA (6.75 micro g/side, P<0.0005) or DHbetaE (3.38 micro
             g/side, P<0.025) caused significant working memory
             impairments. When given together MLA and DHbetaE did not
             produce an additive effect. In fact, the 6.75 micro g/kg
             dose of DHbetaE produced a significant (P<0.0005)
             attenuation of the MLA-induced working memory impairment.
             Significant effects were not seen with reference memory or
             response latency. Nicotinic systems in the basolateral
             amygdala, as in the ventral hippocampus, are important for
             spatial working memory. In both the basolateral amygdala and
             the ventral hippocampus, MLA and DHbetaE individually caused
             working memory impairments. The lowest effective dose of
             DHbetaE was lower in the basolateral amygdala than in the
             ventral hippocampus. In both the basolateral amygdala and
             the ventral hippocampus, combined MLA and DHbetaE treatment
             did not produce additive working memory deficits. Unlike in
             the ventral hippocampus, the addition of DHbetaE to MLA in
             the basolateral amygdala significantly reduced the
             MLA-induced working memory deficit.},
   Doi = {10.1016/s0926-6410(02)00209-4},
   Key = {fds274461}
}

@article{fds274215,
   Author = {Levin, ED},
   Title = {Behavioral Toxicology Society 2002 annual meeting
             report},
   Journal = {Neurotoxicology and Teratology},
   Volume = {25},
   Number = {1},
   Pages = {77-80},
   Publisher = {Elsevier BV},
   Year = {2003},
   Month = {January},
   url = {http://dx.doi.org/10.1016/S0892-0362(02)00355-0},
   Doi = {10.1016/S0892-0362(02)00355-0},
   Key = {fds274215}
}

@article{fds274216,
   Author = {Levin, ED and Chrysanthis, E and Yacisin, K and Linney,
             E},
   Title = {Erratum: Chlorpyrifos exposure of developing zebrafish:
             Effects on survival and long-term effects on response
             latency and spatial discrimination (Neurotoxicology and
             Teratology (2003) 25 (51-57))},
   Journal = {Neurotoxicology and Teratology},
   Volume = {25},
   Number = {5},
   Pages = {639},
   Publisher = {Elsevier BV},
   Year = {2003},
   Month = {January},
   url = {http://dx.doi.org/10.1016/S0892-0362(03)00077-1},
   Doi = {10.1016/S0892-0362(03)00077-1},
   Key = {fds274216}
}

@article{fds274430,
   Author = {Levin, ED and Chrysanthis, E and Yacisin, K and Linney,
             E},
   Title = {Chlorpyrifos exposure of developing zebrafish: effects on
             survival and long-term effects on response latency and
             spatial discrimination.},
   Journal = {Neurotoxicology and Teratology},
   Volume = {25},
   Number = {1},
   Pages = {51-57},
   Year = {2003},
   Month = {January},
   ISSN = {0892-0362},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/12633736},
   Keywords = {Animals • Behavior, Animal • Central Nervous
             System • Chlorpyrifos • Discrimination Learning
             • Disease Models, Animal • Dose-Response
             Relationship, Drug • Embryo, Nonmammalian •
             Embryonic Development • Female • Humans •
             Insecticides • Larva • Pregnancy • Prenatal
             Exposure Delayed Effects* • Reaction Time • Space
             Perception • Survival Rate • Zebrafish • drug
             effects • drug effects* • embryology •
             embryology* • growth & development • growth &
             development* • physiology • physiopathology •
             toxicity*},
   Abstract = {Chlorpyrifos (CPF) is a widely used insecticide, which has
             been shown to interfere with neurobehavioral development.
             Rat models have been key in demonstrating that prenatal CPF
             exposure causes choice accuracy deficits and motor
             alterations, which persist into adulthood. Complementary
             nonmammalian models can be useful in determining the
             molecular mechanisms underlying the persisting behavioral
             effects of developmental CPF exposure. Zebrafish with their
             clear chorion and extensive developmental information base
             provide an excellent model for assessment of molecular
             processes of toxicant impacted neurodevelopment. To
             facilitate the use of the zebrafish model and to compare it
             to the more typical rodent models, the behavioral phenotype
             of CPF toxicity in zebrafish must be well characterized. Our
             laboratory has developed methods for assessing spatial
             discrimination learning in zebrafish, which can
             differentiate response latency from choice accuracy in a
             three chambered fish tank. Low and high doses of CPF (10 and
             100 ng/ml on days 1-5 postfertilization) both had
             significant persisting effects on both spatial
             discrimination and response latency over 18 weeks of
             testing. The high, but not the low dose, significantly
             accelerated mortality rates of the fish during the study
             from 20-38 weeks of age. Developmental exposure to either 10
             or 100 ng/ml of CPF caused significant spatial
             discrimination impairments in zebrafish when they were
             adults. The impairment caused by 10 ng/ml was seen during
             early but not later testing, while the impairment caused by
             100 ng/ml became more pronounced with continued testing. The
             higher dose caused a more pervasive impairment. The 10 and
             100 ng/ml doses had opposite effects on response latency.
             The low 10 ng/ml dose significantly slowed response latency,
             while the high 100 ng/ml dose significant increased response
             latency. Both of these effects diminished with continued
             testing. CPF exposure during early development caused clear
             behavioral impairments, which lasted throughout adulthood in
             zebrafish. The molecular mechanisms by which early
             developmental CPF exposure produces these behavioral
             impairments expressed in adulthood can now be studied in the
             zebrafish model.},
   Doi = {10.1016/s0892-0362(02)00322-7},
   Key = {fds274430}
}

@article{fds274349,
   Author = {Levin, ED},
   Title = {Nicotinic receptor subtypes and cognitive
             function.},
   Journal = {Journal of Neurobiology},
   Volume = {53},
   Number = {4},
   Pages = {633-640},
   Year = {2002},
   Month = {December},
   ISSN = {0022-3034},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/12436426},
   Keywords = {Amygdala • Animals • Cognition • Hippocampus
             • Humans • Memory • Nicotine • Nicotinic
             Agonists • Nicotinic Antagonists • Receptors,
             Nicotinic • drug effects • drug effects* •
             genetics • metabolism • pharmacology •
             pharmacology* • physiology},
   Abstract = {Nicotinic receptor systems are involved in a wide variety of
             behavioral functions including cognitive function. Nicotinic
             medications may provide beneficial treatment for cognitive
             dysfunction such as Alzheimer's disease, schizophrenia, and
             attention deficit hyperactivity disorder (ADHD). Nicotine
             has been shown to improve attentional performance in all of
             these disorders. Better efficacy with fewer side effects
             might be achieved with novel nicotinic ligands selective for
             particular nicotinic subtypes. To develop these novel
             selective nicotinic ligands it is important to use animal
             models to determine the critical neurobehavioral bases for
             nicotinic involvement in cognitive function.
             Nicotine-induced cognitive improvement in rats is most
             consistently seen in working memory tasks. We have found
             that both acute and chronic nicotine administration
             significantly improves working memory performance of rats in
             the radial-arm maze. The pharmacologic and anatomic
             mechanisms for this effect have been examined in our
             laboratory in a series of local drug infusion studies. Both
             alpha 4 beta 2 and alpha 7 nicotinic receptors in the
             ventral hippocampus and basolateral amygdala are involved in
             working memory function. Working memory impairments were
             caused by local infusion of either alpha 4 beta 2 or alpha 7
             antagonists. Ventral hippocampal alpha 4 beta 2
             blockade-induced working memory deficits are reversed by
             chronic systemic nicotine treatment, while ventral
             hippocampal alpha 7 blockade-induced working memory deficits
             were not found to be reversed by the same nicotine regimen.
             Interestingly, alpha 4 beta 2 and alpha 7 induced deficits
             were not found to be additive in either the ventral
             hippocampus or the basolateral amygdala. In fact, in the
             amygdala, alpha 7 antagonist cotreatment actually reversed
             the working memory impairment caused by alpha 4 beta 2
             antagonist administration. These studies of the neural
             nicotinic mechanisms underlying cognitive function are key
             for opening avenues for development of safe and effective
             nicotinic treatments for cognitive dysfunction.},
   Doi = {10.1002/neu.10151},
   Key = {fds274349}
}

@article{fds274382,
   Author = {Rezvani, AH and Bushnell, PJ and Levin, ED},
   Title = {Effects of nicotine and mecamylamine on choice accuracy in
             an operant visual signal detection task in female
             rats.},
   Journal = {Psychopharmacology},
   Volume = {164},
   Number = {4},
   Pages = {369-375},
   Year = {2002},
   Month = {December},
   ISSN = {0033-3158},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/12457266},
   Keywords = {Animals • Attention • Choice Behavior •
             Conditioning, Operant • Contrast Sensitivity •
             Dose-Response Relationship, Drug • Female •
             Mecamylamine • Nicotine • Nicotinic Antagonists
             • Rats • Rats, Sprague-Dawley • Reaction Time
             • Signal Detection (Psychology) • drug effects
             • drug effects* • pharmacology*},
   Abstract = {RATIONALE: During the past decade, central nicotinic systems
             have been shown in both experimental animals and humans to
             play an important role in cognitive function. However, the
             way in which specific aspects of cognitive function are
             affected by nicotinic systems has remained unclear. In
             humans, the most pronounced action of nicotine is to improve
             attention, but in rats, memory improvement is more easily
             seen. This may be due to differences in methods for
             assessing attention in rats and humans or to species
             differences in the roles of nicotinic systems in cognitive
             function. In the current study, we explored the effects of
             nicotine and mecamylamine using an operant visual signal
             detection task designed to model sustained attention
             processes common to rats and humans. METHODS: Adult female
             rats ( n=35) were trained to perform the signal detection
             task to a stable baseline of about 75% accuracy. The rats
             were then assigned to two subgroups of high and low accuracy
             based on overall accuracy (hits and correct rejections) at
             the end of training. All rats were then injected (SC, 10 min
             before testing) with saline or different doses of nicotine
             (0.0125, 0.025, 0.05, 0.1, 0.2 and 0.4 mg/kg) or the
             nicotinic antagonist mecamylamine (1, 2 and 4 mg/kg).
             RESULTS: A low dose range of nicotine (0.0125, 0.025, and
             0.05 mg/kg) caused a dose-related increase in percent
             correct rejection. This dose range did not affect correct
             detections of the signal (percent hit). Higher doses of
             nicotine (0.1, 0.2 and 0.4 mg/kg) did not affect percent
             correct rejection, but did have a time-dependent effect on
             percent hit. Early in the session, the higher doses of
             nicotine reduced percent hit, whereas during the later part
             of the session higher doses of nicotine increased percent
             hit. Effects of nicotine did not differ between the high-
             and low-accuracy rats. Mecamylamine decreased choice
             accuracy, reducing both percent hit and percent correct
             rejection. Mecamylamine reduced percent hit in the
             low-accuracy rats at a lower drug dose than in the
             high-accuracy rats. CONCLUSIONS: These results support the
             involvement of nicotinic systems in attention in rats, as
             has been shown in humans. This rat model of sustained
             attention may provide a good approach to studying neural
             mechanisms underlying the effects of nicotinic cholinergic
             receptors on attention and a means to evaluate the potential
             of novel nicotinic agonists to counteract attentional
             dysfunction.},
   Doi = {10.1007/s00213-002-1221-0},
   Key = {fds274382}
}

@article{fds274473,
   Author = {Levin, ED and Addy, N and Baruah, A and Elias, A and Christopher, NC and Seidler, FJ and Slotkin, TA},
   Title = {Prenatal chlorpyrifos exposure in rats causes persistent
             behavioral alterations.},
   Journal = {Neurotoxicology and Teratology},
   Volume = {24},
   Number = {6},
   Pages = {733-741},
   Year = {2002},
   Month = {November},
   ISSN = {0892-0362},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/12460655},
   Keywords = {Animals • Animals, Newborn • Brain •
             Chlorpyrifos • Cholinergic Fibers • Cholinesterase
             Inhibitors • Cognition Disorders • Dose-Response
             Relationship, Drug • Female • Male • Maze
             Learning • Memory, Short-Term • Mental Disorders
             • Motor Activity • Muscarinic Antagonists •
             Pregnancy • Prenatal Exposure Delayed Effects* •
             Rats • Rats, Sprague-Dawley • Reaction Time •
             Receptors, Muscarinic • Scopolamine • Sex
             Characteristics • chemically induced* • drug
             effects • drug effects* • metabolism •
             pharmacology • physiology • physiopathology •
             toxicity*},
   Abstract = {Use of chlorpyrifos (CPF) has been curtailed due to its
             developmental neurotoxicity. In rats, postnatal CPF
             administration produces lasting changes in cognitive
             performance, but less information is available about the
             effects of prenatal exposure. We administered CPF to
             pregnant rats on gestational days (GD) 17-20, a peak period
             of neurogenesis, using doses (1 or 5 mg/kg/day) below the
             threshold for fetal growth impairment. We then evaluated
             performance in the T-maze, Figure-8 apparatus and 16-arm
             radial maze, beginning in adolescence and continuing into
             adulthood. CPF elicited initial locomotor hyperactivity in
             the T-maze. Females showed slower habituation in the Fig. 8
             maze; no effects were seen in males. In the radial-arm maze,
             females showed impaired choice accuracy for both working and
             reference memory and again, males were unaffected. Despite
             the deficits, all animals eventually learned the maze with
             continued training. At that point, we challenged them with
             the muscarinic antagonist, scopolamine, to determine the
             dependence of behavioral performance on cholinergic
             function. Whereas control females showed impairment with
             scopolamine, CPF-exposed females did not, implying that the
             delayed acquisition of the task had been accomplished
             through alternative mechanisms. The differences were
             specific to muscarinic circuits, as control and CPF groups
             responded similarly to the nicotinic antagonist,
             mecamylamine. Surprisingly, adverse effects of CPF were
             greater in the group receiving 1 mg/kg as compared to 5
             mg/kg. Promotional effects of acetylcholine (ACh) on cell
             differentiation may thus help to offset CPF-induced
             developmental damage that occurs through other
             noncholinergic mechanisms. Our results indicate that late
             prenatal exposure to CPF induces long-term changes in
             cognitive performance that are distinctly gender-selective.
             Additional defects may be revealed by similar strategies
             that subject the animals to acute challenges, thus,
             uncovering the adaptive mechanisms that maintain basal
             performance.},
   Doi = {10.1016/s0892-0362(02)00272-6},
   Key = {fds274473}
}

@article{fds274411,
   Author = {Addy, N and Levin, ED},
   Title = {Nicotine interactions with haloperidol, clozapine and
             risperidone and working memory function in
             rats.},
   Journal = {Neuropsychopharmacology},
   Volume = {27},
   Number = {4},
   Pages = {534-541},
   Year = {2002},
   Month = {October},
   ISSN = {0893-133X},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/12377390},
   Keywords = {Animals • Antipsychotic Agents • Brain •
             Clozapine • Dopamine • Dose-Response Relationship,
             Drug • Drug Interactions • Female •
             Haloperidol • Maze Learning • Memory, Short-Term
             • Neural Pathways • Nicotine • Rats •
             Rats, Sprague-Dawley • Reaction Time • Receptors,
             Dopamine • Risperidone • Schizophrenia •
             adverse effects • antagonists & inhibitors • drug
             effects • drug effects* • drug therapy •
             metabolism • metabolism* • pharmacology* •
             physiology • physiopathology},
   Abstract = {Nicotine has been shown in a variety of studies to improve
             memory performance. The cognitive effects of nicotine are
             particularly important with regard to schizophrenia. In the
             current studies nicotine interactions with three different
             antipsychotic drugs, haloperidol, clozapine and risperidone,
             were assessed with regard to memory function. Female
             Sprague-Dawley rats were trained on the radial-arm maze to
             asymptotic levels of choice accuracy. They were then
             administered nicotine alone or in combination with
             haloperidol, clozapine or risperidone. Acute haloperidol
             (0.04 mg/kg) did not by itself affect memory performance.
             Co-administration of haloperidol with nicotine, however,
             decreased memory performance compared with nicotine
             administration in isolation. Acute clozapine (1.25 and 2.5
             mg/kg) caused a significant memory impairment, an effect
             reversed by acute nicotine co-treatment. Risperidone (0.05
             mg/kg), like haloperidol, did not by itself affect memory
             performance. Risperidone co-administration with nicotine,
             however, did significantly attenuate the improvement caused
             by nicotine administration in isolation. The similar
             interaction of haloperidol and risperidone with nicotine may
             be due to their common action of blocking D(2) receptors, a
             mechanism of action not shared by clozapine. In contrast to
             the interaction of nicotine with haloperidol or risperidone,
             nicotine effectively reversed clozapine-induced memory
             impairment. These studies demonstrate interactions between
             nicotine and antipsychotic drugs in terms of memory, which
             may have important impacts on the treatment of
             schizophrenia.},
   Doi = {10.1016/S0893-133X(02)00327-5},
   Key = {fds274411}
}

@article{fds274438,
   Author = {Levin, ED and Rezvani, AH},
   Title = {Nicotinic treatment for cognitive dysfunction.},
   Journal = {Current Drug Targets. Cns and Neurological
             Disorders},
   Volume = {1},
   Number = {4},
   Pages = {423-431},
   Year = {2002},
   Month = {August},
   ISSN = {1568-007X},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/12769614},
   Keywords = {Alzheimer Disease • Animals • Attention Deficit
             Disorder with Hyperactivity • Cognition Disorders
             • Humans • Nicotinic Agonists • Nicotinic
             Antagonists • Schizophrenia • drug therapy •
             drug therapy* • psychology • therapeutic
             use*},
   Abstract = {Nicotinic medications may provide beneficial therapeutic
             treatment for cognitive dysfunction such as Alzheimer's
             disease, schizophrenia and attention deficit hyperactivity
             disorder (ADHD). For development of nicotinic treatments we
             are fortunate to have a well characterized lead compound,
             nicotine. Transdermal nicotine patches offer a way to
             deliver measured doses of nicotine in a considerably safer
             fashion than the more traditional means of administration,
             tobacco smoking. We have found that transdermal nicotine
             significantly improves attentional function in people with
             Alzheimer's disease, schizophrenia or ADHD as well as normal
             nonsmoking adults. To follow-up on this proof of principal
             that nicotinic treatment of cognitive dysfunction holds
             promise, it is important to use animal models to determine
             the critical neurobehavioral bases for nicotinic involvement
             in cognitive function so that more selective nicotinic
             analogues that improve cognitive function with fewer side
             effects can be developed. We have found with local infusion
             in rat studies that the hippocampus and amygdala are
             important substrates for nicotinic effects on working memory
             function. Both alpha7 and alpha4beta2 nicotinic receptors
             are involved in working memory. Nicotinic interactions with
             dopaminergic and glutaminergic systems are also important in
             the basis of cognitive function. Studies of the neural
             nicotinic mechanisms underlying cognitive function are key
             for opening avenues for development of safe and effective
             nicotinic treatments for cognitive dysfunction.},
   Doi = {10.2174/1568007023339102},
   Key = {fds274438}
}

@article{fds274367,
   Author = {Rezvani, AH and Levin, ED},
   Title = {Nicotine-alcohol interactions and cognitive function in
             rats.},
   Journal = {Pharmacology, Biochemistry, and Behavior},
   Volume = {72},
   Number = {4},
   Pages = {865-872},
   Year = {2002},
   Month = {July},
   ISSN = {0091-3057},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/12062576},
   Keywords = {Animals • Body Temperature • Central Nervous
             System Depressants • Cognition • Dose-Response
             Relationship, Drug • Ethanol • Female •
             Injections, Intraperitoneal • Injections, Subcutaneous
             • Maze Learning • Memory, Short-Term •
             Nicotine • Nicotinic Agonists • Rats • Rats,
             Sprague-Dawley • drug effects • drug effects*
             • pharmacology*},
   Abstract = {Nicotine and ethanol are the most widely abused drugs in the
             world. They are very often used and abused together.
             However, little is known about the functional interaction of
             nicotine and ethanol. The current project studied the
             interactive effects of nicotine and ethanol on working
             memory in the eight-arm radial maze. Adult female rats were
             trained on a radial arm maze for 18 sessions to reach
             asymptotic levels of choice accuracy. During the maintenance
             phase of radial arm maze testing, which indexed working
             memory function, the rats were injected with nicotine (0,
             0.15, 0.3, 0.6, and 1.2 mg/kg sc, 20 min before testing)
             with and without ethanol pretreatment (0 or 1.5 g/kg, 16%
             v/v ip, 30 min before testing). All animals received the
             treatments in a counterbalanced order with at least 1 week
             between treatments. Higher doses of nicotine had a
             significant interaction with ethanol in terms of radial arm
             maze choice accuracy. Nicotine plus ethanol coadministration
             precipitated a significant choice accuracy impairment at
             doses that when given alone had no effect on performance. At
             the lower dose range of nicotine, ethanol coadministration
             eliminated the nicotine-induced memory improvement. No
             significant effects were seen with either nicotine or
             ethanol treatment or their interaction on response latency
             in the radial arm maze. The nicotine-ethanol interactive
             effects on memory were compared with the interaction of
             their well-characterized hypothermic effects. Nicotine and
             alcohol, when injected separately or in combination, induced
             hypothermia with no significant interactive effect. This
             study found that ethanol blocked low-dose nicotine-induced
             memory improvement and precipitated memory impairment with
             high-dose nicotine treatment. This interaction may be an
             important consideration for nicotine and ethanol coabuse and
             the possible therapeutic use of nicotinic drugs for memory
             dysfunction.},
   Doi = {10.1016/s0091-3057(02)00762-1},
   Key = {fds274367}
}

@article{fds316109,
   Author = {Qiao, D and Seidler, FJ and Levin, ED and Padilla, S and Slotkin,
             TA},
   Title = {Developmental neurotoxicity of chlorpyrifos: Defining the
             vulnerable period},
   Journal = {Faseb Journal},
   Volume = {16},
   Number = {5},
   Pages = {A949-A949},
   Publisher = {FEDERATION AMER SOC EXP BIOL},
   Year = {2002},
   Month = {March},
   ISSN = {0892-6638},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000174593901244&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Key = {fds316109}
}

@article{fds274454,
   Author = {Levin, ED and Christopher, NC and Lateef, S and Elamir, BM and Patel, M and Liang, L-P and Crapo, JD},
   Title = {Extracellular superoxide dismutase overexpression protects
             against aging-induced cognitive impairment in
             mice.},
   Journal = {Behavior Genetics},
   Volume = {32},
   Number = {2},
   Pages = {119-125},
   Year = {2002},
   Month = {March},
   ISSN = {0001-8244},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/12036109},
   Keywords = {Aging • Animals • Extracellular Space •
             Female • Gene Expression Regulation, Enzymologic •
             Genotype • Humans • Maze Learning • Mice
             • Mice, Transgenic • Oxidative Stress •
             Retention (Psychology) • Signal Transduction •
             Superoxide Dismutase • enzymology* • genetics
             • genetics* • physiology •
             physiology*},
   Abstract = {Extracellular superoxide dismutase (EC-SOD) controls the
             availability of extracellular superoxide and appears to play
             a role in controlling oxidative stress and intercellular
             signaling. Whether EC-SOD overexpression would help or
             hinder neurobehavioral function appears to depend on the age
             of the individual. In young adult mice, we have found that
             EC-SOD overexpression can interfere with learning on the
             radial-arm maze, possibly by reducing control over nitric
             oxide neurotransmission. In aged mice, we found, in the
             current study, that EC-SOD overexpression greatly improves
             learning on the radial-arm maze. Control (N = 17) and EC-SOD
             overexpressing mice (N = 13) acquired the 8-arm radial maze
             over 21 sessions of training. The EC-SOD overexpressing mice
             had significantly better choice accuracy than the control
             mice (p < 0.005). The EC-SOD overexpressing mice averaged
             6.34+/-0.22 correct arm entries before an error (entries to
             repeat) during the acquisition phase, while the control mice
             averaged 5.18+/-0.22 entries to repeat. EC-SOD genotype did
             not cause a main effect on response latency. The advantage
             held by the EC-SOD overexpressing mice persisted during the
             eight-session post-acquisition phase of testing (p < 0.01).
             When there was a shift from high to low levels of motivation
             by reducing the period of food restriction before testing,
             the EC-SOD overexpression-induced improvement was reduced
             slightly, but it was still significant compared with the
             wild-type controls (p < 0.025). Then, after 4 months of no
             testing, the mice were tested for retention and
             reacquisition of performance on the radial-arm maze. The
             EC-SOD overexpressing mice maintained their significantly
             better choice accuracy (p < 0.05). Enhancement of EC-SOD
             activity appears to improve learning and memory performance,
             specifically in aging mice. EC-SOD mimetic treatment during
             the course of aging may hold promise for aging-induced
             cognitive impairment.},
   Doi = {10.1023/a:1015201823417},
   Key = {fds274454}
}

@article{fds274481,
   Author = {Arthur, D and Levin, ED},
   Title = {Chronic inhibition of alpha4beta2 nicotinic receptors in the
             ventral hippocampus of rats: impacts on memory and nicotine
             response.},
   Journal = {Psychopharmacology},
   Volume = {160},
   Number = {2},
   Pages = {140-145},
   Year = {2002},
   Month = {March},
   ISSN = {0033-3158},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/11875631},
   Keywords = {Alzheimer Disease • Animals • Cognition Disorders
             • Dihydro-beta-Erythroidine • Female •
             Hippocampus • Memory • Nicotine • Nicotinic
             Antagonists • Rats • Rats, Sprague-Dawley •
             Receptors, Nicotinic • Time Factors • antagonists
             & inhibitors • drug effects* • drug therapy •
             metabolism • pharmacology*},
   Abstract = {RATIONALE: Acute and chronic systemic nicotine
             administration has been shown to cause significant spatial
             memory improvement. The critical nicotinic receptor subtypes
             for this effect and their location are still being
             determined. Nicotinic receptors in the ventral hippocampus
             have been found to be critically involved in memory. Acute
             ventral hippocampal infusions of dihydro-beta-erythroidine
             (DHbetaE), an alpha4beta2 nicotinic receptor antagonist,
             impaired spatial memory of rats in the radial-arm maze.
             OBJECTIVES: The current study used chronic ventral
             hippocampal infusion of DHbetaE as a model of nicotinic
             receptor loss such as that which occurs in Alzheimer's
             disease. The therapeutic effect of systemic nicotine
             treatment in reversing the DHbetaE-induced memory impairment
             was determined. METHODS: Rats were pretrained to asymptotic
             levels of performance on the eight-arm radial maze. Then,
             they were implanted with bilateral infusion cannulae in the
             ventral hippocampus, through which 0, 33.3, or 100
             microg/side/day of DHbetaE was continuously infused for 4
             weeks. The rats were retested on the eight-arm maze
             throughout infusion period and after withdrawal, and the
             interaction of acute systemic nicotine injections on memory
             was tested. RESULTS: The higher (100 microg/side/day) but
             not the lower (33.3 microg/side/day) DHbetaE dose caused a
             significant spatial memory impairment. Acute systemic
             nicotine injections (0, 0.1, 0.2, and 0.4 mg/kg,
             subcutaneous) attenuated the memory impairing effects of 100
             microg/side/day of DHbetaE. There was no significant effect
             on response latency with the chronic DHbetaE infusion. Acute
             systemic nicotine infusions did significantly speed
             responding, an effect which was reversed by chronic
             hippocampal infusions of DHbetaE. After withdrawal there
             were no significant lasting effects on choice accuracy or
             response latency. Wet-dog shakes were significantly elevated
             during chronic hippocampal DHbetaE administration with no
             effect during the withdrawal period. CONCLUSIONS: These
             results indicate that chronic inhibition of a subset of
             nicotinic receptors in the hippocampus results in a
             significant impairment in the spatial memory choice
             accuracy. The ability of nicotine to attenuate the
             impairment supports the development of nicotinic agonist
             therapy of syndromes, such as Alzheimer's disease, that
             involve a chronic decrease in the activity of the
             alpha4beta2 nicotinic receptors and memory
             impairment.},
   Doi = {10.1007/s00213-001-0961-6},
   Key = {fds274481}
}

@article{fds316103,
   Author = {Rossler, IB and Johnson, RC and Krystal, AD and Weiner, RD and Levin,
             ED and Logue, P and Coffey, CE and Edwards, CL},
   Title = {A naturalistic study of the effects of smoking on the
             cognitive side effects of ECT.},
   Journal = {The Journal of Ect},
   Volume = {18},
   Number = {1},
   Pages = {64-64},
   Publisher = {LIPPINCOTT WILLIAMS & WILKINS},
   Year = {2002},
   Month = {March},
   ISSN = {1095-0680},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000174804700030&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Key = {fds316103}
}

@article{fds274338,
   Author = {Esposito, E and Cortesi, R and Porta, R and Trento, F and Nastruzzi,
             C},
   Title = {Effect of long-term stabilization of cationic liposomes as
             defibrotide delivery system for antithrombotic
             activity},
   Journal = {Drug Development Research},
   Volume = {55},
   Number = {2},
   Pages = {127-138},
   Publisher = {WILEY},
   Year = {2002},
   Month = {January},
   ISSN = {0272-4391},
   url = {http://dx.doi.org/10.1002/ddr.10041},
   Abstract = {The general goal of this study was to produce cationic
             liposome formulations suitable for the in vivo
             administration of defibrotide (DFT) (a DNA-based drug) and
             to investigate in vitro and in vivo the stability of such a
             formulation. This article describes the freeze-drying of
             cationic liposomes using as cryoprotectants different
             carbohydrates, such as sorbitol, mannitol, and sucrose.
             Liposome characteristics before and after freeze-drying,
             such as size, morphology, and ability in complexing a
             DNA-based drug, have been investigated. The in vitro studies
             indicate that cationic liposomes sufficiently maintain the
             initial characteristics after lyophilization and rehydration
             including the ability to complex DFT. The in vivo data show
             that lyophilized cationic liposome formulations can be
             safely stored for at least 3 months. Before in vivo use,
             liposomes can be rehydrated with DFT solutions, resulting in
             the formation of stable complexes retaining an in vivo
             activity comparable to that of the freshly prepared
             formulation. © 2002 Wiley-Liss, Inc.},
   Doi = {10.1002/ddr.10041},
   Key = {fds274338}
}

@article{fds316085,
   Author = {Levin, ED and Christopher, NC},
   Title = {Persistence of nicotinic agonist RJR 2403-induced working
             memory improvement in rats},
   Journal = {Drug Development Research},
   Volume = {55},
   Number = {2},
   Pages = {97-103},
   Publisher = {WILEY},
   Year = {2002},
   Month = {January},
   ISSN = {0272-4391},
   url = {http://dx.doi.org/10.1002/ddr.10024},
   Abstract = {Nicotinic systems are involved in the neural basis of memory
             function and nicotinic agonists have shown promise for the
             treatment of cognitive dysfunction. Both acute and chronic
             nicotinic treatment has been shown to improve memory
             performance. There is some evidence for the persistence of
             nicotine-induced memory improvements lasting longer than the
             pharmacokinetic presence of nicotine. Novel nicotinic
             agonists may produce the beneficial effects of nicotine on
             cognitive function with fewer side effects. RJR 2403
             (metanicotine or (E)-N-methyl-4-(3-pyridinyl)-3-butene-1-amine)
             a preferential α4β2 nicotinic agonist has been shown in
             previous studies to improve memory function. The present
             study examined the persistence of oral RJR 2403 on memory
             performance in young adult Sprague-Dawley rats (3-5 months
             old) 30 min, 1 h, and 6 h post-administration (PO). In the
             first experiment, the typical inverted U-shaped dose
             response curve for cognitive enhancing drugs was seen with
             RJR 2403 30 min after administration. The lower dose of 1
             mg/kg (3.6 μmol/kg), but not higher doses of 3 or 10 mg/kg
             (10.8 or 36 μmol/kg), of RJR 2403 significantly (P < 0.05)
             improved working memory on the radial-arm maze relative to
             placebo-treated controls. In the second experiment, young
             adult rats were administered RJR 2403 (0, 0.3, or 1.0 mg/kg)
             and tested 1 h or 6 h following administration in separate
             treatment groups. The 0.3 mg/kg RJR 2403 dose (1.08
             αmol/kg) caused a significant (P < 0.05) memory improvement
             1 h after oral administration. Interestingly, both the 0.3
             and 1.0 mg/kg RJR 2403 doses (1.08 and 3.6 μmol/kg)
             significantly (P < 0.05) improved memory six hours after
             administration. These data demonstrate the efficacy of oral
             RJR 2403 in improving cognitive performance and the long
             duration of action of RJR 2403 in young adult rats. In
             contrast, no significant memory improvement was seen in aged
             rats aged (24-26 months old) after RJR 2403 administration.
             The inability of RJR 2403 to enhanced cognitive functions in
             aged rats might be related to the decrease in the number of
             α4β2 nicotinic receptors, which occurs with age. A similar
             decreased responsiveness in aged rats has been seen with
             nicotine. The persistence of action of RJR 2403 provides
             additional promise for its potential as a treatment for
             cognitive dysfunction. However, the decreased responsiveness
             in subjects in populations with decreased nicotinic receptor
             number may limit the effectiveness of nicotinic therapies.
             © 2002 Wiley-Liss, Inc.},
   Doi = {10.1002/ddr.10024},
   Key = {fds316085}
}

@article{fds274344,
   Author = {Levin, ED and Bradley, A and Addy, N and Sigurani,
             N},
   Title = {Hippocampal alpha 7 and alpha 4 beta 2 nicotinic receptors
             and working memory.},
   Journal = {Neuroscience},
   Volume = {109},
   Number = {4},
   Pages = {757-765},
   Year = {2002},
   ISSN = {0306-4522},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/11927157},
   Keywords = {Acetylcholine • Animals • Dihydro-beta-Erythroidine
             • Dose-Response Relationship, Drug • Female •
             Grooming • Hippocampus • Maze Learning •
             Mecamylamine • Memory, Short-Term • Neurons •
             Nicotinic Antagonists • Rats • Rats,
             Sprague-Dawley • Receptors, Nicotinic • Synaptic
             Transmission • cytology • drug effects •
             metabolism • metabolism* • pharmacology •
             pharmacology* • physiology • physiology*},
   Abstract = {Nicotine and other nicotinic receptor agonists have been
             found in a variety of studies to improve memory, while
             nicotinic receptor blockade can impair memory. The critical
             neural mechanisms for nicotinic involvement with memory are
             still under investigation. Initial evidence supports the
             involvement of the ventral hippocampus. Lesions in this area
             block nicotine-induced memory improvement and
             mecamylamine-induced impairment. Local ventral hippocampal
             application of the nicotinic channel blocker mecamylamine
             impairs memory in the 8-arm radial maze. Both alpha 4 beta 2
             and alpha 7 nicotinic receptors seem to be involved. Ventral
             hippocampal infusions of high doses of the alpha 4 beta 2
             nicotinic antagonist dihydro-beta-erythrodine (DH beta E)
             and the alpha 7 nicotinic antagonist methyllycaconitine
             (MLA) impair memory performance on the 8-arm radial maze.
             However, high doses of these drugs may limit specificity and
             they cause preconvulsant effects, which in themselves may
             affect memory. The current study used the more challenging
             16-arm radial maze to determine the effects of lower doses
             of these drugs on memory and to differentiate effects on
             working and reference memory. Adult female Sprague-Dawley
             rats were trained on a working and reference memory task in
             the 16-arm radial maze and then were implanted with
             bilateral chronic guide cannulae directed to the ventral
             hippocampus. After recovery from surgery, the rats received
             acute intrahippocampal infusions of dose combinations of DH
             beta E and MLA. In the first study, DH beta E (0 and 6.75
             microg/side) and MLA (0, 6.75, 13.5 and 27 microg/side) were
             administered in a counter-balanced order. In the second
             study, lower doses of DH beta E (0, 1.6375, 3.275 and 6.75
             microg/side) were administered alone or with MLA (0 and 6.75
             microg/side) in a counter-balanced order. In the first
             study, DH beta E caused a significant increase in both
             working and reference memory errors. MLA at a dose of 27
             microg/side caused a significant increase in working memory
             errors, but this dose had no significant effect on reference
             memory errors. Interestingly, no additive effects were seen
             with combined administration of DH beta E and MLA in this
             study, and at the doses used, no effects were seen on
             response latency. In the second study, lower doses of DH
             beta E did not cause a significant deficit in working memory
             performance. Co-administration of MLA with these
             subthreshold doses did precipitate a memory impairment. The
             current results confirm the specificity of the memory
             deficits caused by these drugs. These results support the
             involvement of alpha 4 beta 2 and alpha 7 nicotinic
             receptors in the ventral hippocampus as being critical for
             memory function.},
   Doi = {10.1016/s0306-4522(01)00538-3},
   Key = {fds274344}
}

@article{fds274408,
   Author = {Bettany, JH and Levin, ED},
   Title = {Ventral hippocampal alpha 7 nicotinic receptor blockade and
             chronic nicotine effects on memory performance in the
             radial-arm maze.},
   Journal = {Pharmacology, Biochemistry, and Behavior},
   Volume = {70},
   Number = {4},
   Pages = {467-474},
   Year = {2001},
   Month = {December},
   ISSN = {0091-3057},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/11796146},
   Keywords = {Aconitine • Animals • Dose-Response Relationship,
             Drug • Female • Hippocampus • Insecticides
             • Maze Learning • Memory • Nicotine •
             Nicotinic Agonists • Nicotinic Antagonists • Rats
             • Rats, Sprague-Dawley • Receptors, Nicotinic
             • administration & dosage* • analogs &
             derivatives* • drug effects* • pharmacology •
             pharmacology* • physiology • physiology*},
   Abstract = {Chronic nicotine administration has been shown to
             significantly improve working memory. Nicotinic involvement
             in memory function critically involves the ventral
             hippocampus. Local ventral hippocampal infusions of the
             nicotinic antagonists mecamylamine, dihydro-beta-erythroidine
             (DH beta E) and methyllycaconitine (MLA) significantly
             impair working memory. The impairment caused by hippocampal
             infusion of the alpha 4 beta 2 antagonist DH beta E is
             reversed by chronic systemic nicotine. This study determined
             the interaction of chronic systemic nicotine with acute
             ventral hippocampal infusions of the alpha 7 antagonist MLA.
             Adult female Sprague-Dawley rats were trained on an 8-arm
             radial maze working memory task. Then they underwent ventral
             hippocampal cannulation and received sc implants of
             minipumps delivering nicotine (0 or 5 mg/kg/day for 28
             days). Acute ventral hippocampal infusions of MLA (0, 4.88,
             14.64 and 43.92 microg/side) were given during 3-4 weeks of
             chronic nicotine. MLA caused a significant dose-related
             memory impairment. In the rats not receiving nicotine, the
             14.64 and 43.92 microg/side MLA doses caused significant
             memory impairment. Chronic systemic nicotine exposure did
             not block the MLA-induced memory impairment. Comparing the
             current results with MLA with previous results with DH beta
             E, equimolar ventral hippocampal DH beta E more effectively
             impaired memory than MLA, but the DH beta E-induced
             impairment was more effectively reversed by chronic systemic
             nicotine administration.},
   Doi = {10.1016/s0091-3057(01)00643-8},
   Key = {fds274408}
}

@article{fds274433,
   Author = {Rezvani, AH and Bushnell, PJ and Burkholder, JM and Glasgow, HB and Levin, ED},
   Title = {Specificity of cognitive impairment from Pfiesteria
             piscicida exposure in rats: attention and visual function
             versus behavioral plasticity.},
   Journal = {Neurotoxicology and Teratology},
   Volume = {23},
   Number = {6},
   Pages = {609-616},
   Year = {2001},
   Month = {November},
   ISSN = {0892-0362},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/11792529},
   Keywords = {Animals • Attention • Discrimination Learning
             • Female • Injections, Subcutaneous • Maze
             Learning • Pfiesteria piscicida • Photic
             Stimulation • Rats • Rats, Sprague-Dawley •
             drug effects* • pathogenicity*},
   Abstract = {Pfiesteria piscicida is a toxic dinoflagellate that has
             caused massive fish kills in estuaries along the East Coast
             of the United States, and exposure of humans to toxic
             Pfiesteria has been associated with cognitive impairment. A
             visual signal detection task was used to determine the
             possible importance of attentional and visual processes in
             Pfiesteria effects on cognitive function. Adult female rats
             were trained to perform the signal detection task. After
             training, the rats were injected subcutaneously with fish
             culture water containing toxic Pfiesteria (35,600 or 106,800
             cells of Pfiesteria/kg of rat body weight) or with (control)
             fish culture water containing no Pfiesteria. Effects of
             toxic Pfiesteria on maintenance of signal detection behavior
             were assessed for 2 weeks after treatment. Then, the
             signal-response contingencies were reversed. After the
             discrimination was reestablished on the reversed levers, the
             rats received a second dose of toxic Pfiesteria. The rats
             were again tested for 2 weeks, after which a second reversal
             was imposed. Pfiesteria did not affect behavior in the
             signal detection task during 2 weeks of prereversal testing
             after either exposure. However, a significant
             Pfiesteria-induced deficit emerged when the signal-response
             contingencies were reversed. These findings suggest that
             Pfiesteria-induced deficits emerge during periods of
             behavioral transition and not during performance of
             previously learned tasks.},
   Doi = {10.1016/s0892-0362(01)00169-6},
   Key = {fds274433}
}

@article{fds274421,
   Author = {Levin, ED},
   Title = {A rat model of the cognitive impairment from Pfiesteria
             piscicida exposure.},
   Journal = {Environmental Health Perspectives},
   Volume = {109 Suppl 5},
   Pages = {757-763},
   Year = {2001},
   Month = {October},
   ISSN = {0091-6765},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/11677185},
   Keywords = {Animals • Cognition Disorders • Disease Models,
             Animal • Environmental Exposure* • Female •
             Maze Learning • Pfiesteria piscicida • Protozoan
             Infections • Rats • Rats, Sprague-Dawley •
             complications* • etiology* • pathogenicity*},
   Abstract = {Pfiesteria piscicida Steidinger & Burkholder, an estuarine
             dinoflagellate known to kill fish, has also been associated
             with neurocognitive deficits in humans. We have developed a
             rat model to determine the cause-and-effect relationship
             between exposure to Pfiesteria-containing water and
             cognitive impairment and to determine the neurobehavioral
             mechanisms underlying the Pfiesteria effect. The rat model
             of Pfiesteria toxicity can also provide important
             information concerning the toxin or toxins responsible for
             neurocognitive deficits resulting from Pfiesteria exposure.
             With the rat model we have repeatedly documented a
             Pfiesteria-induced choice accuracy impairment during
             radial-arm maze learning. The Pfiesteria-induced impairment
             was relatively specific to the acquisition phase of
             training. When rats were pretrained, Pfiesteria treatment
             did not affect performance. However, when these same rats
             were retrained on another task, the Pfiesteria-induced
             impairment became evident. Pfiesteria-induced effects were
             also seen in a locomotor activity test in the figure-8
             apparatus and selected components of the functional
             observational battery. Pfiesteria effects on choice accuracy
             in the radial-arm maze in rats constitute a critical
             component of the model of Pfiesteria toxicity, as the
             hallmark of Pfiesteria toxicity in humans is cognitive
             dysfunction. Our finding that analysis of the first six
             sessions of radial-arm maze testing is sufficient for
             determining the effect means that this test will be useful
             as a rapid screen for identifying the critical neurotoxin(s)
             of Pfiesteria in future studies.},
   Doi = {10.1289/ehp.01109s5757},
   Key = {fds274421}
}

@article{fds274511,
   Author = {Levin, ED and Addy, N and Nakajima, A and Christopher, NC and Seidler,
             FJ and Slotkin, TA},
   Title = {Persistent behavioral consequences of neonatal chlorpyrifos
             exposure in rats.},
   Journal = {Brain Research. Developmental Brain Research},
   Volume = {130},
   Number = {1},
   Pages = {83-89},
   Year = {2001},
   Month = {September},
   ISSN = {0165-3806},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/11557096},
   Keywords = {Animals • Animals, Newborn • Behavior, Animal
             • Chlorpyrifos • Female • Insecticides •
             Male • Maze Learning • Mecamylamine • Memory
             • Motor Activity • Muscarinic Antagonists •
             Nicotinic Antagonists • Pregnancy • Rats •
             Rats, Sprague-Dawley • Scopolamine • drug effects
             • drug effects* • pharmacology •
             pharmacology*},
   Abstract = {Chlorpyrifos (CPF) is a widely used insecticides which has
             been shown to alter brain cell development. The current
             project was conducted to determine whether there are
             persistent behavioral effects of early [1 mg/kg/day
             postnatal days (PNDs) 1-4] or late (5 mg/kg/day PNDs 11-14)
             postnatal CPF exposure in rats. We tested spontaneous
             alternation in a T-maze, locomotor activity in the Figure-8
             apparatus and learning in the 16-arm radial maze, throughout
             adolescence and into adulthood. Exposure during either
             neonatal period elicited significant long-term effects on
             cognitive behavior. In the radial-arm maze, as has been seen
             previously, control male performed more accurately than
             control females. Early postnatal CPF exposure reversed this
             effect. With exposure on PNDs 1-4, females in the CPF group
             showed a reduction in working and reference memory errors in
             the radial maze, reducing their error rate to that seen in
             control males; in contrast, CPF-exposed males exhibited an
             increase in errors during the initial stages of training.
             When animals were exposed on PNDs 11-14 and then tested in
             adolescence and adulthood, males showed a significant
             slowing of response latency in the T-maze and the rate of
             habituation in the Figure-8 apparatus was slowed in both
             sexes. When females were challenged acutely with the
             muscarinic antagonist, scopolamine, they did not show
             reference memory impairment, whereas controls did; these
             results suggest that adaptations occur after CPF exposure
             that lead to loss of muscarinic cholinergic control of
             reference memory. No such changes were seen with a nicotinic
             cholinergic antagonist (mecamylamine). These results
             indicate that early neonatal exposure to CPF induces
             long-term changes in cognitive performance that, in keeping
             with the neurochemical changes seen previously, are
             distinctly gender-selective. Additional defects may be
             revealed by similar strategies that subject the animals to
             acute challenges, thus uncovering the adaptive mechanisms
             that maintain basal performance.},
   Doi = {10.1016/s0165-3806(01)00215-2},
   Key = {fds274511}
}

@article{fds274482,
   Author = {Levin, ED and Conners, CK and Silva, D and Canu, W and March,
             J},
   Title = {Effects of chronic nicotine and methylphenidate in adults
             with attention deficit/hyperactivity disorder.},
   Journal = {Experimental and Clinical Psychopharmacology},
   Volume = {9},
   Number = {1},
   Pages = {83-90},
   Year = {2001},
   Month = {February},
   ISSN = {1064-1297},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/11519638},
   Keywords = {Adult • Attention • Attention Deficit Disorder
             with Hyperactivity • Central Nervous System Stimulants
             • Depressive Disorder • Female • Humans
             • Male • Memory • Methylphenidate •
             Middle Aged • Nicotine • Nicotinic Agonists •
             Psychiatric Status Rating Scales • Psychomotor
             Performance • drug effects • drug therapy* •
             psychology • therapeutic use*},
   Abstract = {Acute nicotine treatment has been found to reduce symptoms
             of attention deficit/hyperactivity disorder in adults (E. D.
             Levin, C. K. Conners, et al., 1996). In this study, chronic
             nicotine effects were compared with placebo and
             methylphenidate. Acute and chronic nicotine treatment
             significantly attenuated the rise in hit reaction time
             standard error over session blocks on the Conners Continuous
             Performance Test (C. K. Conners et al., 1996). Acute
             nicotine significantly reduced severity of clinical symptoms
             on the Clinical Global Impressions scale (National Institute
             of Mental Health, 1985). Nicotine caused a significant
             decrease in self-report of depressive mood as measured by
             the Profile of Mood States test (D. M. McNair, M. Lorr, & L.
             F. Droppleman, 1981). This small study (40 participants)
             provided evidence that nicotine treatment can reduce
             severity of attentional deficit symptoms and produce
             improvement on an objective computerized attention
             task.},
   Doi = {10.1037/1064-1297.9.1.83},
   Key = {fds274482}
}

@article{fds274485,
   Author = {Rezvani, AH and Levin, ED},
   Title = {Cognitive effects of nicotine.},
   Journal = {Biological Psychiatry},
   Volume = {49},
   Number = {3},
   Pages = {258-267},
   Year = {2001},
   Month = {February},
   ISSN = {0006-3223},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/11230877},
   Keywords = {Adult • Aged • Alzheimer Disease • Animals
             • Cognition Disorders • Hippocampus • Humans
             • Neuropsychological Tests* • Nicotine •
             Receptors, Nicotinic • Treatment Outcome • drug
             effects • drug therapy* • therapeutic
             use*},
   Abstract = {Nicotine and other nicotinic agonists have been found to
             improve performance on attention and memory tasks. Clinical
             studies using nicotine skin patches have demonstrated the
             efficacy of nicotine in treating cognitive impairments
             associated with Alzheimer's disease, schizophrenia, and
             attention-deficit/hyperactivity disorder. Experimental
             animal studies have demonstrated the persistence of
             nicotine-induced working memory improvement with chronic
             exposure, in addition to the efficacy of a variety of
             nicotinic agonists. Mechanistic studies have found that
             alpha7 and alpha4beta2 nicotinic receptors in the
             hippocampus are critical for nicotinic involvement in
             cognitive function. Clinical and experimental animal studies
             provide mutually supporting information for the development
             of novel nicotinic therapies for cognitive
             dysfunction.},
   Doi = {10.1016/s0006-3223(00)01094-5},
   Key = {fds274485}
}

@article{fds274340,
   Author = {Arthur, D and Levin, ED},
   Title = {Spatial and non-spatial visual discrimination learning in
             zebrafish (danio rerio)},
   Journal = {Animal Cognition},
   Volume = {4},
   Number = {2},
   Pages = {125-131},
   Publisher = {Springer Nature},
   Year = {2001},
   Month = {January},
   url = {http://dx.doi.org/10.1007/s100710100111},
   Abstract = {Zebrafish (Danio rerio) provide an excellent model for
             assessment of molecular processes of neurodevelopment. To
             determine the functional importance of molecular events
             during neurodevelopment, we have developed methods for
             assessing learning in zebrafish in a three-chambered fish
             tank. In the first study, simple escape response was
             assessed. Zebrafish tested with a moving net learned to
             escape to another chamber more rapidly over the six sessions
             of training than the fish with the still net which did not
             learn. Upon reversal of the contingencies, the fish switched
             to the inactive net rapidly learned to suppress the escape
             response and fish formerly in the inactive net condition
             learned to avoid the moving net. In the second study,
             spatial discrimination learning was assessed. Zebrafish were
             trained on a right-left position discrimination to avoid the
             active net. Zebrafish showed significant improvement in
             escape responses over six sessions of training with three
             trials per session. In the third study, red-blue non-spatial
             discrimination learning was assessed. There was a
             significant improvement over the first six training
             sessions. With the reversal of contingencies, there was a
             significant decline of performance. With continued training,
             the fish again significantly improved avoidance. These
             studies found an effective motivational stimulus and
             procedure for studying escape behavior in zebrafish; a
             procedure whereby zebrafish would learn both spatial and
             non-spatial discrimination. These methods are being
             developed to help determine the functional importance of
             molecular events during zebrafish neurodevelopment. ©
             Springer-Verlag 2001.},
   Doi = {10.1007/s100710100111},
   Key = {fds274340}
}

@article{fds136383,
   Title = {Rezvani AH and ED Levin. Cognitive effects of nicotine.
             Biological Psychiatry. 49:258-267, 2001.},
   Year = {2001},
   Key = {fds136383}
}

@article{fds136384,
   Title = {Arthur D and ED Levin. Spatial and non-spatial
             discrimination learning in zebrafish (Danio rerio) Animal
             Cognition, 4:125-131, 2001.},
   Year = {2001},
   Key = {fds136384}
}

@article{fds136385,
   Title = {Levin ED, A Bradley N Addy and N Sigurani. Hippocampal (7
             and (4(2 nicotinic receptors and working memory.
             Neuroscience. In press.},
   Year = {2001},
   Key = {fds136385}
}

@article{fds136386,
   Title = {Levin ED and NC Christopher. Persistence of nicotinic
             agonist RJR 2403 induced working memory improvement in rats.
             Drug Development Research, In press.},
   Year = {2001},
   Key = {fds136386}
}

@article{fds136387,
   Title = {Levin ED and AH Rezvani. Nicotinic Involvement in Memory
             Function of Rats. In: Nicotinic Receptors in the Nervous
             System. ED Levin (ed.), CRC Press, New York, 167-178
             2001.},
   Year = {2001},
   Key = {fds136387}
}

@article{fds136388,
   Title = {Levin ED. Nicotine Effects on Attention Deficit
             Hyperactivity Disorder. In: Nicotinic Receptors in the
             Nervous System. ED Levin (ed.), CRC Press, New York,
             251-260, 2001.},
   Year = {2001},
   Key = {fds136388}
}

@article{fds136389,
   Title = {Book Nicotinic Receptors in the Nervous System. ED Levin
             (ed.), CRC Press, New York, 2001.},
   Year = {2001},
   Key = {fds136389}
}

@article{fds136401,
   Title = {Levin ED, N Addy, A Nakajima, NC Christopher, FJ Seidler and
             TA Slotkin Persistent behavioral consequences of neonatal
             chlorpyrifos exposure in rats. Developmental Brain Research,
             130:83-89, 2001.},
   Year = {2001},
   Key = {fds136401}
}

@article{fds136402,
   Title = {Levin ED, A rat model of the cognitive impairment from
             Pfiesteria piscicida exposure. Environmental Health
             Perspectives, 109(Suppl. 5):757-763, 2001.},
   Year = {2001},
   Key = {fds136402}
}

@article{fds136403,
   Title = {Rezvani AH, PJ Bushnell, JM Burkholder, HB Glasgow, Jr. and
             ED Levin. Specificity of cognitive impairment from
             Pfiesteria piscicida exposure in rats: Attention and visual
             function vs. behavioral plasticity. Neurotoxicology and
             Teratology. 23:609-616, 2001.},
   Year = {2001},
   Key = {fds136403}
}

@article{fds136404,
   Title = {Levin ED. Nicotinic Systems: An Integrated Approach. In:
             Nicotinic Receptors in the Nervous System. ED Levin (ed.),
             CRC Press, New York, 281-282, 2001.},
   Year = {2001},
   Key = {fds136404}
}

@article{fds274467,
   Author = {Levin, ED and Mead, T and Rezvani, AH and Rose, JE and Gallivan, C and Gross, R},
   Title = {The nicotinic antagonist mecamylamine preferentially
             inhibits cocaine vs. food self-administration in
             rats.},
   Journal = {Physiology & Behavior},
   Volume = {71},
   Number = {5},
   Pages = {565-570},
   Year = {2000},
   Month = {December},
   ISSN = {0031-9384},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/11239676},
   Keywords = {Animals • Cocaine • Conditioning, Operant •
             Dopamine Uptake Inhibitors • Eating • Female
             • Food • Mecamylamine • Nicotinic Antagonists
             • Rats • Rats, Sprague-Dawley • Reinforcement
             (Psychology) • Self Administration •
             administration & dosage • drug effects • drug
             effects* • pharmacology*},
   Abstract = {Nicotinic acetylcholine systems play important roles in
             addiction, and nicotinic receptor stimulation stimulates
             dopamine release while the nicotinic antagonist mecamylamine
             reduces it. Reid et al. [Neuropsychopharmacology 20 (1999)
             297.] recently found in human cocaine addicts that
             mecamylamine reduced cue-elicited cocaine craving. The
             current study assessed the impact of mecamylamine on cocaine
             self-administration in rats. Female Sprague-Dawley rats
             (N=7) were implanted with intravenous (iv) catheters and
             trained to lever press for cocaine (0.32 mg/kg/infusion FR-1
             with a 60-s timeout) in 45-min sessions. After 2 weeks of
             training, the rats were injected with saline or mecamylamine
             (1, 2, or 4 mg/kg sc) 10 min before the session. They
             received the same dose for 1 week with 1 week of uninjected
             testing between doses. Mecamylamine, compared to saline,
             significantly (P<.05) reduced the number of cocaine
             infusions per session with each of these doses. This effect
             did not appear to be due to a generalized reduction in
             behavioral activity. Another set of female Sprague-Dawley
             rats (N=8) were trained to lever press for food
             reinforcement. In these rats, the 1 and 2-mg/kg mecamylamine
             doses had no effect on food self-administration. Significant
             reductions in food self-administration were not seen unless
             the high dose of 4-mg/kg mecamylamine was used. Nicotinic
             antagonist treatment reduces cocaine self-administration in
             rats at doses that do not cause generalized effects on
             food-reinforced responding. Nicotinic antagonistic treatment
             may be a useful new approach to treat cocaine
             addiction.},
   Doi = {10.1016/s0031-9384(00)00382-6},
   Key = {fds274467}
}

@article{fds274414,
   Author = {Bancroft, A and Levin, ED},
   Title = {Ventral hippocampal alpha4beta2 nicotinic receptors and
             chronic nicotine effects on memory.},
   Journal = {Neuropharmacology},
   Volume = {39},
   Number = {13},
   Pages = {2770-2778},
   Year = {2000},
   Month = {October},
   ISSN = {0028-3908},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/11044746},
   Keywords = {Animals • Behavior, Animal • Dihydro-beta-Erythroidine
             • Female • Hippocampus • Maze Learning •
             Memory • Memory, Short-Term • Nicotine •
             Nicotinic Agonists • Nicotinic Antagonists • Rats
             • Rats, Sprague-Dawley • Receptors, Nicotinic
             • drug effects • drug effects* • metabolism
             • pharmacology • pharmacology*},
   Abstract = {Chronic nicotine administration has been repeatedly shown to
             facilitate working memory function in rats on the radial-arm
             maze. The critical neural mechanisms for this effect are
             still being discovered. The nicotinic nature of the chronic
             nicotine induced memory improvement is supported by the
             finding that it is blocked by chronic mecamylamine
             co-infusion. The hippocampus also appears to be critically
             important. Hippocampal ibotenic acid lesions block the
             effect. Within the hippocampus, we have found that the
             alpha4beta2 nicotinic receptor subtype is involved in memory
             functioning. Acute ventral hippocampal infusions of the
             alpha4beta2 nicotinic antagonist dihydro-beta-erythroidine
             (DHbetaE) significantly decreased working memory performance
             in the radial-arm maze. The aim of the current study was to
             determine the importance of alpha4beta2 receptors within the
             ventral hippocampus for the memory enhancing effects of
             chronic nicotine treatment. Adult female Sprague-Dawley rats
             were trained on the 8-arm radial maze and were cannulated
             bilaterally in the ventral hippocampus. Osmotic minipumps
             administering chronic nicotine at a rate of 5 mg per kg per
             day were also implanted in the nicotine treatment rats.
             Control rats received saline-only minipumps. For a period of
             4 weeks after surgery, each rat received bilateral
             hippocampal infusions of 0, 2, 6 and 18 microg per side of
             DHbetaE and tested for memory performance on the radial-arm
             maze. Radial-arm maze choice accuracy was impaired by acute
             hippocampal DHbetaE infusion in a dose-related fashion. This
             acute hippocampal DHbetaE-induced choice accuracy impairment
             was eliminated by chronic systemic nicotine infusion.
             Chronic nicotine in combination with acute vehicle
             hippocampal infusion was not seen to alter choice accuracy.
             Response latency was not found to be altered by acute
             hippocampal DHbetaE in the absence of chronic nicotine
             administration, but it did attenuate the response latency
             reduction induced by chronic nicotine infusion. Wet dog
             shakes were not found to be affected by hippocampal DHbetaE
             when given without chronic nicotine. Wet dog shakes were
             significantly increased by chronic nicotine infusion.
             Intra-hippocampal DHbetaE significantly potentiated this
             effect. The results from the current study reinforce the
             hypothesis that ventral hippocampal alpha4beta2 nicotinic
             receptors are important for memory function. These receptors
             may also have a role to play in the development of other
             aspects of behavior associated with chronic nicotine
             treatment.},
   Doi = {10.1016/s0028-3908(00)00099-x},
   Key = {fds274414}
}

@article{fds274504,
   Author = {Narahashi, T and Fenster, CP and Quick, MW and Lester, RA and Marszalec,
             W and Aistrup, GL and Sattelle, DB and Martin, BR and Levin,
             ED},
   Title = {Symposium overview: mechanism of action of nicotine on
             neuronal acetylcholine receptors, from molecule to
             behavior.},
   Journal = {Toxicological Sciences},
   Volume = {57},
   Number = {2},
   Pages = {193-202},
   Year = {2000},
   Month = {October},
   ISSN = {1096-6080},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/11006350},
   Keywords = {Animals • Anthelmintics • Dose-Response
             Relationship, Drug • Drug Interactions • Ethanol
             • Hippocampus • Humans • Insecticides •
             Memory • Neurons • Nicotine • Receptors,
             Nicotinic • Up-Regulation • drug effects •
             drug effects* • genetics • metabolism •
             metabolism* • pharmacology • pharmacology*},
   Abstract = {Nicotine has long been known to interact with nicotinic
             acetylcholine (ACh) receptors since Langley used it
             extensively to chart sympathetic ganglia a century ago. It
             has also been used as an effective insecticide. However, it
             was not until the 1990s that the significance of nicotine
             was increasingly recognized from the toxicological,
             pharmacological, and environmental points of view. This is
             partly because studies of neuronal nicotinic ACh receptors
             are rapidly emerging from orphan status, fueled by several
             lines of research. Since Alzheimer's disease is known to be
             associated with down-regulation of cholinergic activity in
             the brain, a variety of nicotine derivatives are being
             tested and developed for treatment of the disease. Public
             awareness of the adverse effects of nicotine has reached the
             highest level recently. Since insect resistance to
             insecticides is one of the most serious issues in the
             pest-control arena, it is an urgent requirement to develop
             new insecticides that act on target sites not shared by the
             existing insecticides. The neuronal nicotinic ACh receptor
             is one of them, and new nicotinoids are being developed.
             Thus, the time is ripe to discuss the mechanism of action of
             nicotine from a variety of angles, including the molecular,
             physiological, and behavioral points of view. This Symposium
             covered a wide area of nicotine studies: genetic, genomic,
             and functional aspects of nicotinic ACh receptors were
             studied, as related to anthelmintics and insecticides;
             interactions between ethanol and nicotine out the ACh
             receptor were analyzed, in an attempt to explain the
             well-known heavy drinker-heavy smoker correlation; the
             mechanisms that underlie the desensitization of ACh
             receptors were studied as related to nicotine action;
             selective pharmacological profiles of nicotine, and
             descriptions of some derivatives were described; and chronic
             nicotine infusion effects on memory were examined using
             animal models.},
   Doi = {10.1093/toxsci/57.2.193},
   Key = {fds274504}
}

@article{fds274360,
   Author = {Rusted, JM and Newhouse, PA and Levin, ED},
   Title = {Nicotinic treatment for degenerative neuropsychiatric
             disorders such as Alzheimer's disease and Parkinson's
             disease.},
   Journal = {Behavioural Brain Research},
   Volume = {113},
   Number = {1-2},
   Pages = {121-129},
   Year = {2000},
   Month = {August},
   ISSN = {0166-4328},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/10942039},
   Keywords = {Alzheimer Disease • Animals • Brain • Humans
             • Nicotinic Agonists • Parkinson Disease •
             Receptors, Nicotinic • Treatment Outcome • adverse
             effects • drug effects • drug therapy* •
             therapeutic use*},
   Abstract = {Nicotinic systems play an important role in the neural basis
             of working memory and attention. Recent progress in
             understanding of the structure, function, and distribution
             of central nervous system (CNS) nicotinic receptors and
             their pharmacology has opened up new possibilities for novel
             CNS therapeutics with nicotinic agents. In this paper, we
             review the theoretical justification and the experimental
             evidence supporting these developments. We focus on the
             applications of nicotinic agonists in CNS disorders that are
             degenerative in nature, namely Parkinson's disease and
             Alzheimer's disease. We suggest that there is considerable
             potential for therapeutic applications in the near future.
             Clinically, two major issues remain: (a) the selectivity of
             effects, that is, developing compounds which are selective
             in producing improvement in cognition, motor function,
             attention, or pain without significant side-effects; and (b)
             the realistic likelihood of long-term improvements in
             everyday functioning in people who have degenerative
             diseases.},
   Doi = {10.1016/s0166-4328(00)00207-2},
   Key = {fds274360}
}

@article{fds274509,
   Author = {White, AM and Ghia, AJ and Levin, ED and Swartzwelder,
             HS},
   Title = {Binge pattern ethanol exposure in adolescent and adult rats:
             differential impact on subsequent responsiveness to
             ethanol.},
   Journal = {Alcoholism, Clinical and Experimental Research},
   Volume = {24},
   Number = {8},
   Pages = {1251-1256},
   Year = {2000},
   Month = {August},
   ISSN = {0145-6008},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/10968665},
   Keywords = {Aging* • Animals • Behavior, Animal • Body
             Weight • Ethanol • Male • Memory • Rats
             • Rats, Sprague-Dawley • administration & dosage*
             • drug effects • pharmacology},
   Abstract = {BACKGROUND: Recent evidence indicates that adolescent
             animals are more sensitive than adults to the disruptive
             effects of acute ethanol exposure on spatial learning. It is
             not yet known whether adolescent animals are also more
             sensitive than adults to the enduring neurobehavioral
             effects of repeated ethanol exposure. In this study, animals
             were exposed to ethanol in a binge-pattern during either
             adolescence or adulthood. At a time when all subjects were
             adults, spatial working memory was examined in the absence
             and presence of an acute ethanol challenge. METHODS: Rats
             were exposed to ethanol (5.0 g/kg intraperitoneally) or
             isovolumetric saline at 48 hr intervals over 20 days.
             Exposure began on either postnatal day 30 (adolescent group)
             or 70 (adult group). Twenty days after the final injection,
             a time at which all animals were adults, the subjects were
             tested on an elevated plus maze and then were trained to
             perform a spatial working memory task on an eight-arm radial
             maze. At the beginning of each session of training on the
             working memory task, subjects retrieved food rewards on four
             of the eight arms. After a delay, subjects were placed on
             the maze and allowed to retrieve food from the remaining
             four arms. RESULTS: Prior exposure to ethanol did not
             influence behavior on the plus maze. Performance of the
             groups did not differ during acquisition of the spatial
             working memory task with a 5 min delay or during subsequent
             testing with a 1 hr delay. However, animals treated with
             ethanol during adolescence exhibited larger working memory
             impairments during an ethanol challenge (1.5 g/kg
             intraperitoneally) than subjects in the other three groups.
             CONCLUSIONS: The findings indicate that binge pattern
             exposure to ethanol during adolescence enhances
             responsiveness to the memory-impairing effects of ethanol in
             adulthood.},
   Doi = {10.1097/00000374-200008000-00017},
   Key = {fds274509}
}

@article{fds274361,
   Author = {Bushnell, PJ and Levin, ED and Marrocco, RT and Sarter, MF and Strupp,
             BJ and Warburton, DM},
   Title = {Attention as a target of intoxication: insights and methods
             from studies of drug abuse.},
   Journal = {Neurotoxicology and Teratology},
   Volume = {22},
   Number = {4},
   Pages = {487-502},
   Year = {2000},
   Month = {July},
   ISSN = {0892-0362},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/10974587},
   Keywords = {Animals • Attention • Cocaine • Humans •
             Mental Disorders • Nicotine • Pharmaceutical
             Preparations • Substance-Related Disorders •
             adverse effects • adverse effects* • drug effects*
             • physiology • physiopathology},
   Abstract = {A symposium was convened to discuss recent developments in
             the assessment of attention and the effects of drugs and
             toxic chemicals on attention at the 17th annual meeting of
             the Behavioral Toxicology Society on May 1, 1999, in
             Research Triangle Park, NC. Speakers addressed issues
             including the methodology of assessing cognitive function,
             the neurobiology of specific aspects of attention, the dual
             roles of attention as a target of intoxication and as a
             mediating variable in the development of addiction to
             psychoactive drugs, the changes in attention that accompany
             neuropsychological disorders of schizophrenia, senile
             dementia of the Alzheimer type and attention deficit
             hyperactivity disorder, and potential therapies for these
             disorders. This article provides an overview of the
             objectives of the symposium, followed by summaries of each
             of the talks given.},
   Doi = {10.1016/s0892-0362(00)00077-5},
   Key = {fds274361}
}

@article{fds274474,
   Author = {Levin, ED and Rezvani, AH and Christopher, NC and Glasgow, HB and Deamer-Melia, NJ and Burkholder, JM and Moser, VC and Jensen,
             K},
   Title = {Rapid neurobehavioral analysis of Pfiesteria piscicida
             effects in juvenile and adult rats.},
   Journal = {Neurotoxicology and Teratology},
   Volume = {22},
   Number = {4},
   Pages = {533-540},
   Year = {2000},
   Month = {July},
   ISSN = {0892-0362},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/10974591},
   Keywords = {Aging • Animals • Behavior, Animal • Female
             • Male • Maze Learning • Motor Activity
             • Pfiesteria piscicida* • Protozoan Infections,
             Animal • Rats • Rats, Sprague-Dawley •
             physiology • physiology* • physiopathology*},
   Abstract = {The estuarine dinoflagellate Pfiesteria piscicida is known
             to kill fish and has been associated with neurocognitive
             deficits in humans. We have developed a rat model to
             demonstrate that exposure to Pfiesteria causes significant
             learning impairments. This has been repeatedly seen as a
             choice accuracy impairment during radial-arm maze learning.
             Pfiesteria-induced effects were also seen in a locomotor
             activity test in the figure-8 apparatus. The current studies
             used the short-term radial-arm maze acquisition, the
             figure-8 activity test, and the functional observational
             battery (FOB) to assess Pfiesteria-induced neurobehavioral
             effects in adult and juvenile rats. In study 1, the
             neurobehavioral potency of three different Pfiesteria
             cultures (Pf 113, Pf 728, and Pf Vandermere) was assessed.
             Ninety-six (12 per group) adult female Sprague-Dawley rats
             were injected subcutaneously with a single dose of
             Pfiesteria taken from aquarium-cultured Pfiesteria (35,600
             or 106,800 Pfiesteria cells per kilogram of rat body
             weight). One control group (N = 12) was injected with saline
             and one (N = 12) with aquarium water not containing
             Pfiesteria. All three of the Pfiesteria samples (p < 0.05)
             impaired choice accuracy over the first six sessions of
             training. At the time of the radial-arm maze choice accuracy
             impairment, no overt Pfiesteria-related effects were seen
             using an FOB, indicating that the Pfiesteria-induced choice
             accuracy deficit was not due to generalized debilitation. In
             the figure-8 apparatus, Pfiesteria treatment caused a
             significant decrease in mean locomotor activity. In study 2,
             the neurobehavioral effects of the Pf 728 sample type were
             assessed in juvenile rats. Twenty-four day-old male and
             female rats were injected with 35,600 or 106,800 Pf-728
             Pfiesteria cells per kilogram of rat body weight. As with
             adult females, the juvenile rats showed a significant
             impairment in radial-arm maze choice accuracy. No changes in
             locomotor activity or the FOB were detected in the juvenile
             rats. Furthermore, there were no differences between male
             and female rats in the Pfiesteria-induced choice accuracy
             impairment. Pfiesteria effects on choice accuracy in the
             radial-arm maze in rats constitute a critical component of
             the model of Pfiesteria toxicity, because the hallmark of
             Pfiesteria toxicity in humans is cognitive dysfunction. Our
             finding that analysis of the first six sessions of
             radial-arm maze testing is sufficient for determining the
             effect means that this test will be useful as a rapid screen
             for identifying the critical neurotoxin(s) of Pfiesteria in
             future studies.},
   Doi = {10.1016/s0892-0362(00)00080-5},
   Key = {fds274474}
}

@article{fds274436,
   Author = {Grilly, DM and Simon, BB and Levin, ED},
   Title = {Nicotine enhances stimulus detection performance of middle-
             and old-aged rats: a longitudinal study.},
   Journal = {Pharmacology, Biochemistry, and Behavior},
   Volume = {65},
   Number = {4},
   Pages = {665-670},
   Year = {2000},
   Month = {April},
   ISSN = {0091-3057},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/10764920},
   Keywords = {Aging • Animals • Cognition • Conditioning,
             Operant • Cues • Dose-Response Relationship, Drug
             • Longitudinal Studies • Male • Nicotine
             • Nicotinic Agonists • Photic Stimulation •
             Psychomotor Performance • Rats • Rats, Inbred F344
             • drug effects • drug effects* •
             pharmacology* • psychology*},
   Abstract = {The effects of nicotine on sustained attention were tested
             in F344xBN male rats when they were chronologically middle
             and old aged. The rats (n = 11) were trained in a
             two-choice, stimulus detection task in which a press of one
             of two levers was reinforced with food, with the correct
             lever indicated by the position of a briefly illuminated
             light. They were tested when they were 24-25 and 34-35
             months of age (i.e., at 60-68% and 85-95%, respectively of
             their expected median life span) after saline or 0.1-0.5
             mg/kg doses of nicotine (SC). A significant dose-related
             improvement in percent correct choices and decrease in
             choice response times was found at both ages, and there was
             no significant main effect of age or an age by dose
             interaction. These results support the position that
             nicotine can enhance attentional processes in rats
             throughout their life span. Nicotine and other nicotinic
             agonists may have efficacy in the treatment of disorders
             such as Alzheimer's disease.},
   Doi = {10.1016/s0091-3057(99)00259-2},
   Key = {fds274436}
}

@article{fds274457,
   Author = {Levin, ED and Rezvani, AH},
   Title = {Development of nicotinic drug therapy for cognitive
             disorders.},
   Journal = {European Journal of Pharmacology},
   Volume = {393},
   Number = {1-3},
   Pages = {141-146},
   Year = {2000},
   Month = {March},
   ISSN = {0014-2999},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/10771007},
   Keywords = {Adult • Alzheimer Disease • Animals •
             Attention • Attention Deficit Disorder with
             Hyperactivity • Cognition Disorders • Disease
             Models, Animal • Drug Design • Humans •
             Learning • Memory • Nicotine • Nicotinic
             Agonists • Rats • Schizophrenia • Smoking
             • drug effects • drug therapy • drug therapy*
             • pharmacology • therapeutic use*},
   Abstract = {Nicotine, as well as other nicotinic drugs, may provide
             useful therapeutic treatment for a variety of cognitive
             impairments including those found in Alzheimer's disease,
             schizophrenia and attention deficit hyperactivity disorder
             (ADHD). We have found that nicotine skin patches
             significantly improve attentional performance in people with
             these disease states as well as normal nonsmoking adults.
             Animal models are critical for determining the
             neurobehavioral bases for nicotinic effects on cognitive
             function. We have found in lesion and local infusion studies
             with rats that the hippocampus is an important substrate for
             nicotinic effects on working memory function. Both alpha7
             and alpha4beta2 nicotinic receptors in the hippocampus are
             involved. Further work has investigated the relationship of
             nicotinic systems with dopaminergic and glutaminergic
             systems in the basis of cognitive function. Nicotine has
             proven to be a useful prototypic compound for the family of
             nicotinic compounds. It produces cognitive improvements in
             both animal models and clinical populations. Recent work
             with more selective nicotinic receptor agonists and
             antagonists in animal models is providing important
             information concerning the neural mechanisms for nicotinic
             involvement in cognitive function and opening avenues for
             development of safe and effective nicotinic treatments for
             clinical use.},
   Doi = {10.1016/s0014-2999(99)00885-7},
   Key = {fds274457}
}

@article{fds274447,
   Author = {Levin, ED and Brucato, FH and Crapo, JD},
   Title = {Molecular overexpression of extracellular superoxide
             dismutase increases the dependency of learning and memory
             performance on motivational state.},
   Journal = {Behavior Genetics},
   Volume = {30},
   Number = {2},
   Pages = {95-100},
   Year = {2000},
   Month = {March},
   ISSN = {0001-8244},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/10979599},
   Keywords = {Animals • Appetitive Behavior • Extracellular
             Space • Female • Food Deprivation • Gene
             Expression Regulation, Enzymologic • Maze Learning
             • Mental Recall • Mice • Motivation* •
             Superoxide Dismutase • enzymology • genetics*
             • physiology • physiology*},
   Abstract = {Extracellular superoxide dismutase (EC-SOD) controls the
             availability of extracellular superoxide and appears to play
             a role in controlling intercellular signaling. In this role
             EC-SOD can have potent effects on neurobehavioral function.
             In previous studies, we have found that either over- or
             under-expression of EC-SOD in mice significantly impairs
             spatial learning on the radial-arm maze. In the current
             study, the neurobehavioral nature of the EC-SOD role in
             cognitive function was determined. EC-SOD overexpression
             altered the relationship between both learning and memory
             with motivational state. Mice were tested in the radial-arm
             maze under a high motivational state (22-24 hours of food
             restriction) or a low motivational state (4-6 hours of food
             restriction). Under a high motivational state, the EC-SOD
             overexpressing mice were able to learn in the radial-arm
             maze, albeit at a slightly lower rate than wild-type
             controls. This contrasts with the failure to learn by EC-SOD
             overexpressing mice in our previous study conducted with the
             low motivational state. The change in motivational state did
             not significantly alter the learning rate of controls.
             Similarly, during postacquisition memory phase of testing,
             the EC-SOD overexpressing mice were significantly worse than
             controls when tested in a low motivational state but not
             under a high motivation state. As with learning,
             motivational state did not significantly affect memory
             performance in controls. This study shows that mice with
             EC-SOD overexpression are not incapable of learning and
             memory in the radial-arm maze, but that the mechanisms which
             allow control animals to perform this task well under low
             motivational states are deficient in the mice with EC-SOD
             overexpression.},
   Doi = {10.1023/a:1001947003299},
   Key = {fds274447}
}

@article{fds274214,
   Author = {Keller, JM and Meyer, JN and Mattie, M and Augspurger, T and Rau, M and Dong, J and Levin, ED},
   Title = {Assessment of immunotoxicology in wild populations: Review
             and recommendations},
   Journal = {Reviews in Toxicology},
   Volume = {3},
   Number = {1-4},
   Pages = {167-212},
   Year = {1999},
   Month = {December},
   Abstract = {A heightened recognition of the immunotoxicity of many
             xenobiotics has sparked increased interest in studying
             immune system effects in wildlife. Immunotoxicological
             endpoints have been directly informative in assessing the
             health of wildlife populations themselves, and wildlife
             could also potentially be used as indicators of human and
             ecosystem health. However, the lack of standard methods and
             information regarding normal ranges of immune system
             parameters makes field assessments of wildlife immunological
             status difficult. Compounding this difficulty is the
             unfamiliarity of most wildlife toxicologists with the
             complex immune system and the wide array of methods
             available to study immunotoxicity. This restricts the number
             of studies carried out and further limits the growth of a
             wildlife immunological database. The purpose of this review
             is to facilitate the study of immunological endpoints by
             wildlife toxicologists by presenting 1) an overview of
             immunotoxicology from a biomedical perspective with an
             emphasis on the fundamentals of the immune system and the
             tools/assays available for measuring its function; 2) a
             limited review of applied immunotoxicity studies in wild
             fish, birds, and mammals; and 3) recommendations for
             expanding immunological assessments in wildlife.},
   Key = {fds274214}
}

@article{fds274507,
   Author = {Levin, ED and Bettegowda, C and Blosser, J and Gordon,
             J},
   Title = {AR-R17779, and alpha7 nicotinic agonist, improves learning
             and memory in rats.},
   Journal = {Behavioural Pharmacology},
   Volume = {10},
   Number = {6-7},
   Pages = {675-680},
   Year = {1999},
   Month = {November},
   ISSN = {0955-8810},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/10780509},
   Keywords = {Animals • Bridged Compounds • Female •
             Learning • Maze Learning • Memory • Memory,
             Short-Term • Nicotinic Agonists • Rats •
             Rats, Sprague-Dawley • Receptors, Nicotinic •
             Spiro Compounds • drug effects • drug effects*
             • pharmacology*},
   Abstract = {Nicotinic acetylcholine systems have been found to be
             important for learning and memory function. The prototypic
             nicotinic agonist nicotine has been shown in a variety of
             studies to improve aspects of cognitive function. The
             specific involvement of nicotinic receptor subtypes is now
             being investigated. The involvement of alpha7 nicotinic
             receptors was assessed in this project using a novel alpha7
             nicotinic agonist, AR-R 17779. Repeated doses (subcutaneous
             injection 20 min before testing) of the racemic mixture AR-R
             13489 and its active isomer AR-R 17779 were assessed in
             adult female Sprague-Dawley rats using the eight-arm radial
             maze. AR-R 13489 (2 mg/kg) caused a significant improvement
             of long-term win-shift acquisition after 3 weeks of training
             (n = 10 per group). The same dose of AR-R 17779 also caused
             a significant improvement in repeated acquisition within
             each daily session in the radial-arm maze. In another study,
             the active isomer AR-R 17779 significantly improved
             radial-arm maze working memory function in rats with lesions
             to the septohippocampal projection. Fimbria-fornix lesions
             significantly impaired working memory performance and AR-R
             17779 significantly reversed that impairment. These studies
             showed that alpha7 nicotinic agonist treatment improved
             learning in two radial-arm maze tasks and reversed working
             memory impairment caused by fimbria-fornix sections,
             providing evidence for alpha7 involvement in learning and
             memory, and the potential therapeutic use of AR-R
             17779.},
   Doi = {10.1097/00008877-199911000-00014},
   Key = {fds274507}
}

@article{fds274212,
   Author = {Levin, ED and Lippiello, P},
   Title = {Mutually potentiating effects of mecamylamine and
             haloperidol in producing catalepsy in rats},
   Journal = {Drug Development Research},
   Volume = {47},
   Number = {2},
   Pages = {90-96},
   Publisher = {WILEY},
   Year = {1999},
   Month = {August},
   ISSN = {0272-4391},
   url = {http://dx.doi.org/10.1002/(SICI)1098-2299(199906)47:2<90::AID-DDR4>3.0.CO;2-5},
   Abstract = {Haloperidol and other dopaminergic (DA) blockers have long
             been known to induce catalepsy. Recently, it has been
             reported that nicotine potentiates the cataleptic effect of
             haloperidol. However, this presents a quandary in terms of
             neural interactions between nicotinic and DA systems.
             Nicotine promotes the release of DA in the striatum, which
             should attenuate haloperidol-induced catalepsy. To resolve
             this quandary, we assessed haloperidol interactions with
             nicotine and its antagonist mecamylamine in five studies.
             With low to moderate doses, we did not find that nicotine
             potentiated haloperidol-induced catalepsy. However, in two
             different studies we found that mecamylamine, a nicotinic
             antagonist, significantly potentiated the
             haloperidol-induced catalepsy. This effect was seen with a
             dose of mecamylamine which, by itself, did not have any
             cataleptic effect. These results demonstrate that nicotinic
             receptor blockade effectively potentiates catalepsy caused
             by DA blockade. This suggests that previously seen nicotine-
             induced potentiation of catalepsy may have been due to its
             desensitizing effect. Perhaps the use of nicotinic
             antagonists such as mecamylamine or nicotine + mecamylamine
             combinations would provide a useful adjunct to DA antagonist
             therapy in motor disorders such as Tourette's
             syndrome.},
   Doi = {10.1002/(SICI)1098-2299(199906)47:2<90::AID-DDR4>3.0.CO;2-5},
   Key = {fds274212}
}

@article{fds274213,
   Author = {Levin, ED and Imad Damaj and M and Glassco, W and May, EL and Martin,
             BR},
   Title = {Bridged nicotine, isonicotine, and norisonicotine effects on
             working memory performance of rats in the radial-arm
             maze},
   Journal = {Drug Development Research},
   Volume = {46},
   Number = {2},
   Pages = {107-111},
   Publisher = {WILEY},
   Year = {1999},
   Month = {May},
   ISSN = {0272-4391},
   url = {http://dx.doi.org/10.1002/(SICI)1098-2299(199902)46:2<107::AID-DDR3>3.0.CO;2-C},
   Abstract = {Nicotine and other nicotinic agonists have been found tO
             improve performance in a variety of tasks, including the
             radial-arm maze to improve memory. There has been an active
             effort to develop novel nicotinic agonists for the treatment
             of cognitive dysfunction such as is seen in Alzheimer's
             disease. These novel ligands can also serve as tools with
             which to increase our knowledge concerning the involvement
             of nicotinic systems with cognitive function. The current
             studies were conducted to assess the actions of three new
             nicotinic agonists, i.e., bridged nicotine, isonicotine, and
             norisonicotine, on choice accuracy in the radial-arm maze.
             Rats were trained on a win-shift working memory task in the
             eight-arm radial maze. In Experiment 1, the rats were
             administered (subcutaneously) saline and three doses of
             bridged nicotine, isonicotine, and norisonicotine (0.5, 1.5,
             and 4.5 mg/kg). Bridged nicotine did not cause any
             significant effects on memory performance, although it did
             significantly increase latency and at the high dose caused
             severe slowing and nonperformance. Both isonicotine and
             norisonicotine caused a significant linear dose-related
             improvement in choice accuracy, indicative of improved
             working memory function. In Experiment 2, another set of
             rats received the effective doses of 4.5 mg/kg of
             isonicotine and norisonicotine as well as higher doses of
             13.5 mg/kg of each compound. These doses were administered
             alone or in combination with 5 mg/kg of the nicotinic
             antagonist mecamylamine to determine the nicotinic nature of
             the effects. As in Experiment 1 the 4.5 mg/kg of isonicotine
             caused a significant memory improvement. The 4.5 mg/kg dose
             of norisonicotine caused a more modest rise in performance,
             which was not significantly different from control in this
             experiment. When both experiments were considered together,
             the 4.5 mg/kg doses of both isonicotine and norisonicotine
             were the most effective in improving working memory
             performance. Significant improvements in working memory were
             seen with both drugs (P < 0.025). The higher doses of 13.5
             mg/kg of both isonicotine and norisonicotine resulted in
             nearly control-level performance. Thus, the typical inverted
             U-shaped dose-effect function was evident for both
             isonicotine and norisonicotine. Mecamylamine brought
             performance improved by the 4.5 mg/kg dose back to control
             levels, providing evidence for the nicotinic nature of the
             effect. Both isonicotine and norisonicotine show promise for
             development as memory-improving nicotinic agonist
             drugs.},
   Doi = {10.1002/(SICI)1098-2299(199902)46:2<107::AID-DDR3>3.0.CO;2-C},
   Key = {fds274213}
}

@article{fds274496,
   Author = {Levin, ED and Simon, BB and Schmechel, DE and Glasgow, HB and Deamer-Melia, NJ and Burkholder, JM and Moser, VC and Jensen, K and Harry, GJ},
   Title = {Pfiesteria toxin and learning performance.},
   Journal = {Neurotoxicology and Teratology},
   Volume = {21},
   Number = {3},
   Pages = {215-221},
   Year = {1999},
   Month = {May},
   ISSN = {0892-0362},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/10386824},
   Keywords = {Animals • Female • Humans • Maze Learning
             • Motor Activity • Pfiesteria piscicida •
             Protozoan Infections • Rats • Rats, Sprague-Dawley
             • Time Factors • pathogenicity* • physiology*
             • physiopathology • psychology},
   Abstract = {Pfiesteria piscicida is an estuarine dinoflagellate involved
             with fish kills along the east coast of the United States.
             We previously documented a radial-arm maze learning deficit
             in rats exposed to Pfiesteria that may be related to
             cognitive deficits seen in humans after accidental
             Pfiesteria exposure. The current study elucidated important
             behavioral parameters of this deficit. There were six dose
             groups. Forty (10/group) adult female Sprague-Dawley rats
             were injected (s.c.) with a single dose of Pfiesteria taken
             from aquarium-cultured Pfiesteria (35,600, 106,800, or
             320,400 Pfiesteria cells/kg of rat body weight or a
             cell-free filtrate of the 106,800 cells/kg dose). One
             control group (N = 10) was injected with saline and one (N =
             10) with aquarium water not containing Pfiesteria. Half of
             the rats in each group were tested on an 8-arm radial maze
             in a standard test room, and the other half were tested on
             the radial maze in a sound-attenuating chamber. In the
             standard maze room, there was a significant effect of
             Pfiesteria (p < 0.05) impairing choice accuracy improvement
             over the first six sessions of training among rats
             administered 106,800, 320,400, and the 106,800 cells/kg
             filtered sample. In contrast, there was no indication of an
             effect of Pfiesteria when the rats were tested on the same
             configuration radial maze in the sound-attenuating chamber.
             After 18 sessions of training in one room, the rats were
             switched for six sessions of testing in the other room and
             finally were switched back to their original room for three
             sessions. There was a significant Pfiesteria-induced deficit
             when the rats were tested in the standard test room but not
             when they were tested in the sound-attenuating chamber. When
             the Pfiesteria-exposed rats were initially switched from the
             sound-attenuating chamber to the standard test room they
             performed significantly worse than controls, whereas
             Pfiesteria-treated rats switched from the standard test room
             to the sound-attenuating chamber did not perform differently
             from controls. These results suggest that the
             Pfiesteria-induced learning impairment may result from the
             negative impact of distracting stimuli. At the time of the
             learning impairment, no overt Pfiesteria-related effects
             were seen using a functional observational battery and no
             overall response latency effects were seen, indicating that
             the Pfiesteria-induced choice accuracy deficit was not due
             to generalized debilitation. In the initial use of the
             figure-8 maze in this line of research, the rats in the same
             Pfiesteria treatment groups that showed significant deficits
             in the radial-arm maze showed greater declines in activity
             rates in a 1-h figure-8 locomotor activity test. Both the
             106,800 and 320,400 Pfiesteria cells/kg groups showed
             significantly greater linear trends of activity decline
             relative to tank water-treated controls. This reflected an
             initial slight hyperactivity in the Pfiesteria-treated
             animals followed by a decrease to control levels. Pfiesteria
             effects in the figure-8 maze and in early radial-arm maze
             training may be useful in a rapid screen for identifying the
             critical toxin(s) of Pfiesteria in future
             studies.},
   Doi = {10.1016/s0892-0362(98)00041-5},
   Key = {fds274496}
}

@article{fds274343,
   Author = {White, HK and Levin, ED},
   Title = {Four-week nicotine skin patch treatment effects on cognitive
             performance in Alzheimer's disease.},
   Journal = {Psychopharmacology},
   Volume = {143},
   Number = {2},
   Pages = {158-165},
   Year = {1999},
   Month = {April},
   ISSN = {0033-3158},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/10326778},
   Keywords = {Administration, Cutaneous • Aged • Aged, 80 and
             over • Alzheimer Disease • Attention •
             Cognition • Female • Humans • Male •
             Memory • Middle Aged • Nicotine • Nicotinic
             Agonists • Psychomotor Performance • Treatment
             Outcome • administration & dosage • drug effects
             • drug effects* • drug therapy* • psychology*
             • therapeutic use*},
   Abstract = {RATIONALE: Acute nicotine injections have been found to
             improve attentional performance in patients with Alzheimer's
             disease (AD), but little is known about chronic nicotine
             effects. OBJECTIVE: The present study was undertaken to
             evaluate the clinical and neuropsychological effects of
             chronic transdermal nicotine in Alzheimer's disease subjects
             over a 4-week period. METHODS: The double-blind, placebo
             controlled, cross-over study consisted of two 4-week periods
             separated by a 2-week washout period. Patients wore the
             nicotine patch (Nicotrol) for 16 h a day at the following
             doses: 5 mg/day during week 1, 10 mg/day during weeks 2 and
             3 and 5 mg/day during week 4. The eight subjects had mild to
             moderate AD and were otherwise healthy. RESULTS: Nicotine
             significantly improved attentional performance as measured
             by the Conners' continuous performance test (CPT). There was
             a significant reduction in errors of omission on the CPT
             which continued throughout the period of chronic nicotine
             administration. The variability of hit reaction time
             (reaction time for correct responses) on the CPT was also
             significantly reduced by chronic nicotine. Nicotine did not
             improve performance on other tests measuring motor and
             memory function. CONCLUSIONS: The sustained improvement in
             attention found in this study with nicotine dermal patches
             is encouraging. However, the lack of detected effects of
             nicotine treatment on other cognitive and behavioral domains
             in this study leaves questions concerning the clinical
             impact of nicotinic treatment in Alzheimer's disease. The
             modest size of this study limited statistical power which
             may have been needed to detect more subtle but clinically
             significant cognitive effects. Higher doses of nicotine,
             other nicotinic ligands or combination treatment of nicotine
             with other therapies may be efficacious for producing
             broader therapeutic effects.},
   Doi = {10.1007/s002130050931},
   Key = {fds274343}
}

@article{fds316084,
   Author = {Gingras, JL and Leatherman, NE and Cutler, AR and Levin,
             ED},
   Title = {Nicotine and/or cocaine alters postnatal ventilatory control
             in the rat pup gestationally exposed},
   Journal = {Pediatric Research},
   Volume = {45},
   Number = {4},
   Pages = {51A-51A},
   Publisher = {INT PEDIATRIC RESEARCH FOUNDATION, INC},
   Year = {1999},
   Month = {April},
   ISSN = {0031-3998},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000079476700294&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Key = {fds316084}
}

@article{fds274443,
   Author = {Wilkerson, A and Levin, ED},
   Title = {Ventral hippocampal dopamine D1 and D2 systems and spatial
             working memory in rats.},
   Journal = {Neuroscience},
   Volume = {89},
   Number = {3},
   Pages = {743-749},
   Year = {1999},
   Month = {March},
   ISSN = {0306-4522},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/10199609},
   Keywords = {(R)-2,3,4,5-Tetrahydro-8-chloro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol
             • Animals • Dopamine • Dopamine Agonists
             • Dopamine Antagonists • Dose-Response
             Relationship, Drug • Female • Hippocampus •
             Maze Learning • Memory • Phenanthridines •
             Quinpirole • Raclopride • Rats • Rats,
             Sprague-Dawley • Receptors, Dopamine D1 •
             Receptors, Dopamine D2 • Salicylamides • Spatial
             Behavior • agonists • antagonists & inhibitors
             • drug effects • drug effects* • pharmacology
             • physiology*},
   Abstract = {The hippocampus has long been known to be important for
             memory function. However, the involvement of hippocampal
             dopamine systems with memory has received little attention.
             In the current study, dopamine D1 and D2 hippocampal
             receptor system involvement with memory was assessed in
             female Sprague-Dawley rats by local infusion of D1 and D2
             agonists and antagonists into the ventral hippocampus.
             Working memory performance was assessed on the radial-arm
             maze. Neither the D1 agonist dihydrexidine (1.1-10
             microg/side) nor the D1 antagonist SCH 23390 (0.19-1.67
             microg/side) was effective in significantly altering
             radial-arm maze choice accuracy. In contrast, there were
             significant and opposite effects of D2 agonist and
             antagonist treatments. The D2 agonist quinpirole caused a
             significant (P<0.05) dose-related improvement in choice
             accuracy over a dose range of 1.1-10 microg/side. In a
             complementary fashion, the D2 antagonist raclopride caused a
             significant (P<0.05) dose-related choice accuracy deficit
             over a range of 0.19-1.67 microg/side. This study provides
             clear evidence that hippocampal D2 activity is positively
             related to working memory performance, while evidence for D1
             systems is less compelling. Dopamine D2 receptors in the
             ventral hippocampus were shown to have important influences
             on spatial working memory. In a consistent pattern of
             effects ventral hippocampal infusion of the D2 agonist
             quinpirole improved working memory performance in the
             radial-arm maze, while ventral hippocampal infusion of the
             D2 antagonist raclopride impaired performance.},
   Doi = {10.1016/s0306-4522(98)00346-7},
   Key = {fds274443}
}

@article{fds274480,
   Author = {Gainetdinov, RR and Wetsel, WC and Jones, SR and Levin, ED and Jaber, M and Caron, MG},
   Title = {Role of serotonin in the paradoxical calming effect of
             psychostimulants on hyperactivity.},
   Journal = {Science (New York, N.Y.)},
   Volume = {283},
   Number = {5400},
   Pages = {397-401},
   Year = {1999},
   Month = {January},
   ISSN = {0036-8075},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/9888856},
   Keywords = {Animals • Attention Deficit Disorder with Hyperactivity
             • Behavior, Animal • Carrier Proteins •
             Central Nervous System Stimulants • Corpus Striatum
             • Dopamine • Dopamine Plasma Membrane Transport
             Proteins • Fluoxetine • Humans • Hyperkinesis
             • Maze Learning • Membrane Glycoproteins •
             Membrane Transport Proteins* • Mice • Mice, Inbred
             C57BL • Mice, Knockout • Motor Activity •
             Nerve Tissue Proteins* • Norepinephrine Plasma Membrane
             Transport Proteins • Serotonin • Serotonin Plasma
             Membrane Transport Proteins • Serotonin Uptake
             Inhibitors • Symporters* • Synaptic Transmission*
             • antagonists & inhibitors • drug effects •
             drug therapy • drug therapy* • genetics •
             metabolism • metabolism* • pharmacology •
             pharmacology* • physiology • physiology* •
             physiopathology • psychology},
   Abstract = {The mechanism by which psychostimulants act as calming
             agents in humans with attention-deficit hyperactivity
             disorder (ADHD) or hyperkinetic disorder is currently
             unknown. Mice lacking the gene encoding the plasma membrane
             dopamine transporter (DAT) have elevated dopaminergic tone
             and are hyperactive. This activity was exacerbated by
             exposure to a novel environment. Additionally, these mice
             were impaired in spatial cognitive function, and they showed
             a decrease in locomotion in response to psychostimulants.
             This paradoxical calming effect of psychostimulants depended
             on serotonergic neurotransmission. The parallels between the
             DAT knockout mice and individuals with ADHD suggest that
             common mechanisms may underlie some of their behaviors and
             responses to psychostimulants.},
   Doi = {10.1126/science.283.5400.397},
   Key = {fds274480}
}

@article{fds274501,
   Author = {Levin, ED and Christopher, NC and Weaver, T and Moore, J and Brucato,
             F},
   Title = {Ventral hippocampal ibotenic acid lesions block chronic
             nicotine-induced spatial working memory improvement in
             rats.},
   Journal = {Brain Research. Cognitive Brain Research},
   Volume = {7},
   Number = {3},
   Pages = {405-410},
   Year = {1999},
   Month = {January},
   ISSN = {0926-6410},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/9838204},
   Keywords = {Animals • Conditioning (Psychology) • Drug
             Interactions • Excitatory Amino Acid Agonists •
             Female • Hippocampus • Ibotenic Acid • Maze
             Learning • Memory, Short-Term • Nicotine •
             Nicotinic Agonists • Rats • Rats, Sprague-Dawley
             • Reaction Time • drug effects • drug
             effects* • pharmacology* • physiology},
   Abstract = {Chronic nicotine infusions have been found to significantly
             improve working memory performance in the radial-arm maze.
             This effect is blocked by co-infusions of the nicotinic
             antagonist mecamylamine. Acute nicotine injections also
             improve working memory performance in the radial-arm maze.
             This effect is also blocked by mecamylamine
             co-administration. Recent local infusions studies have
             demonstrated the importance of the ventral hippocampus for
             nicotinic involvement in memory. Local infusions of
             mecamylamine, DHbetaE or MLA impair working memory
             performance on the radial-arm maze. The current study was
             conducted to determine the importance of the ventral
             hippocampus for the chronic effects of nicotine. Rats were
             trained on the working memory task in an eight-arm radial
             maze. After acquisition they underwent either infusions of
             ibotenic acid lesions or vehicle infusions and received
             subcutaneous implants of osmotic minipumps that delivered
             either nicotine at a dose of 5 mg kg-1 day-1 or vehicle in a
             2x2 design. The rats then were given 2 days of recovery and
             were tested on the radial-arm maze three times per week for
             the next 4 weeks. As seen in previous studies, in the sham
             lesioned group nicotine infusions caused a significant
             improvement in choice accuracy. In contrast no
             nicotine-induced improvement was seen in the rats after
             ibotenic acid lesions of the ventral hippocampus. The effect
             of nicotine was blocked even though this lesion did not
             cause a deficit in performance. Previous work showed that
             chronic nicotine infusion still caused a significant
             improvement in working memory performance in the radial-arm
             maze after knife-cut lesions of the fimbria-fornix carrying
             the septo-hippocampal cholinergic innervation. Thus it
             appears that it is the postsynaptic nicotinic receptors in
             the ventral hippocampus which are critically important for
             the expression of the chronic nicotine induced working
             memory improvement.},
   Doi = {10.1016/s0926-6410(98)00044-5},
   Key = {fds274501}
}

@article{fds136400,
   Title = {Gainetinov RR, WW Wetsel, SR Jones, ED Levin, M Jaber and MG
             Caron. Role of serotonin in the paradoxical calming effect
             of psychostimulants on hyperactivity. Science, 283:397-401,
             1999.},
   Year = {1999},
   Key = {fds136400}
}

@article{fds274398,
   Author = {Levin, ED and Bettegowda, C and Weaver, T and Christopher,
             NC},
   Title = {Nicotine-dizocilpine interactions and working and reference
             memory performance of rats in the radial-arm
             maze.},
   Journal = {Pharmacology, Biochemistry, and Behavior},
   Volume = {61},
   Number = {3},
   Pages = {335-340},
   Year = {1998},
   Month = {November},
   ISSN = {0091-3057},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/9768569},
   Keywords = {Animals • Dizocilpine Maleate • Drug Interactions
             • Excitatory Amino Acid Antagonists • Female
             • Maze Learning • Memory • Memory Disorders
             • Nicotine • Nicotinic Agonists • Psychomotor
             Performance • Rats • Rats, Sprague-Dawley •
             administration & dosage • drug effects • drug
             effects* • drug therapy • pharmacology •
             pharmacology* • therapeutic use},
   Abstract = {Both nicotinic cholinergic and NMDA glutaminergic systems
             are important for memory function. Nicotine has been found
             repeatedly to significantly improve working memory
             performance in the radial-arm maze. The NMDA antagonist
             dizocilpine has been found to impair working memory
             performance. There is neuropharmacological evidence that
             these two systems are functionally related. Nicotine is
             potent at releasing many transmitters including glutamate.
             The current study was conducted to examine the interaction
             of nicotinic and NMDA systems with regard to working and
             reference memory. Rats were trained on a working/reference
             procedure on a 16-arm radial maze. After acquisition, they
             were administered nicotine (0, 0.2, and 0.4 mg/kg) and
             dizocilpine (0, 100, and 200 microg/kg) alone or in
             combination in a repeated measures, counterbalanced design.
             As seen previously, nicotine at a dose of 0.2 mg/kg caused a
             significant improvement in working but not reference memory
             performance in the radial-arm maze. The 200 microg/kg dose
             of dizocilpine made the rats nonresponsive on the maze so
             that choice accuracy could not be assessed. The 100
             microg/kg dose of dizocilpine caused significant impairments
             in both working and reference memory. The 0.4 mg/kg dose of
             nicotine significantly attenuated the dizocilpine-induced
             deficit in both working and reference memory. NMDA blockade
             impairs working and reference memory and blocks the
             expression of the working memory improvement caused by 0.2
             mg/kg of nicotine. However, a higher dose of 0.4 mg/kg of
             nicotine is effective at attenuating the dizocilpine-induced
             deficit, even though this dose alone is not effective in
             improving performance. A second study examined the effects
             of a lower dose range of dizocilpine. Comensurately smaller
             memory impairments were seen with lower doses of dizocilpine
             down to 12.5 microg/kg, which did not produce any
             significant effects on memory performance or response
             latency. Nicotine had a more modest effect in attenuating
             the smaller deficits caused by these lower doses of
             dizocilpine. These studies provide evidence for important
             interactions between nicotinic and NMDA systems with regard
             to memory function.},
   Doi = {10.1016/s0091-3057(98)00109-9},
   Key = {fds274398}
}

@article{fds274484,
   Author = {Levin, ED and Conners, CK and Silva, D and Hinton, SC and Meck, WH and March, J and Rose, JE},
   Title = {Transdermal nicotine effects on attention.},
   Journal = {Psychopharmacology},
   Volume = {140},
   Number = {2},
   Pages = {135-141},
   Year = {1998},
   Month = {November},
   ISSN = {0033-3158},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/9860103},
   Keywords = {Administration, Cutaneous • Adolescent • Adult
             • Attention • Attention Deficit Disorder with
             Hyperactivity • Double-Blind Method • Female
             • Humans • Male • Nicotine •
             administration & dosage* • drug effects* • drug
             therapy • pharmacology},
   Abstract = {Nicotine has been shown to improve attentiveness in smokers
             and attenuate attentional deficits in Alzheimer's disease
             patients, schizophrenics and adults with
             attention-deficit/hyperactivity disorder (ADHD). The current
             study was conducted to determine whether nicotine
             administered via transdermal patches would improve
             attentiveness in non-smoking adults without attentional
             deficits. The subjects underwent the nicotine and placebo
             exposure in a counterbalanced double-blind manner. Measures
             of treatment effect included the Profile of Mood States
             (POMS), Conners' computerized Continuous Performance Test
             (CPT) of attentiveness and a computerized interval-timing
             task. The subjects were administered a 7 mg/day nicotine
             transdermal patch for 4.5 h during a morning session.
             Nicotine significantly increased self-perceived vigor as
             measured by the POMS test. On the CPT, nicotine
             significantly decreased the number of errors of omission
             without causing increases in either errors of commission or
             correct hit reaction time. Nicotine also significantly
             decreased the variance of hit reaction time and the
             composite measure of attentiveness. This study shows that,
             in addition to reducing attentional impairment, nicotine
             administered via transdermal patches can improve
             attentiveness in normal adult non-smokers.},
   Doi = {10.1007/s002130050750},
   Key = {fds274484}
}

@article{fds274448,
   Author = {Levin, ED and Brady, TC and Hochrein, EC and Oury, TD and Jonsson, LM and Marklund, SL and Crapo, JD},
   Title = {Molecular manipulations of extracellular superoxide
             dismutase: functional importance for learning.},
   Journal = {Behavior Genetics},
   Volume = {28},
   Number = {5},
   Pages = {381-390},
   Year = {1998},
   Month = {September},
   ISSN = {0001-8244},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/9926619},
   Keywords = {Animals • Brain • Extracellular Space •
             Female • Gene Expression Regulation, Enzymologic •
             Genotype* • Humans • Male • Maze Learning
             • Mental Recall • Mice • Mice, Knockout
             • Mice, Transgenic • Nitric Oxide Synthase •
             Pregnancy • Retention (Psychology) • Superoxide
             Dismutase • enzymology • enzymology* •
             genetics* • physiology • physiology*},
   Abstract = {Extracellular superoxide dismutase (EC-SOD) controls the
             availability of extracellular superoxide (O2.-), which is
             important for a variety of physiological pathways, including
             the primary means of inactivating nitric oxide (NO). The
             role of EC-SOD in neurobehavioral function has been until
             now unexplored. In the current studies, the phenotypic
             expression of genotypic alterations of EC-SOD production in
             mice were characterized for spatial learning and memory.
             Dramatic impairments in spatial learning in the win-shift
             8-arm radial maze were seen in both EC-SOD knockout mice and
             EC-SOD overexpressing mice. The EC-SOD overexpressing mice
             were further characterized as having significant deficits in
             a repeated acquisition task in the radial-arm maze, which
             permitted the dissociation of long and short-term learning.
             Long-term learning was significantly impared by EC-SOD
             overexpression, whereas short-term learning was not
             significantly affected by EC-SOD overexpression. No systems
             have been shown to be importantly involved in learning and
             memory. This may be important in the current studies because
             EC-SOD has primary control over the inactivation of NO. We
             found that EC-SOD overexpressing mice were resistant to the
             cognitive effects of L-NAME (NG-nitro-L-arginine methyl
             ester hydrochloride), an NO synthase inhibitor. Decreased NO
             catabolism in these mice may have served to counter the
             effects of NOS inhibition by L-NAME. The current finding
             that EC-SOD levels that were either higher or lower than
             controls impaired learning demonstrates that the proper
             control of brain extracellular O2.- may be more vital than
             merely reduction of brain extracellular O2.- in maintaining
             adequate learning function.},
   Doi = {10.1023/a:1021673703129},
   Key = {fds274448}
}

@article{fds274492,
   Author = {Levin, ED and Simon, BB},
   Title = {Nicotinic acetylcholine involvement in cognitive function in
             animals.},
   Journal = {Psychopharmacology},
   Volume = {138},
   Number = {3-4},
   Pages = {217-230},
   Year = {1998},
   Month = {August},
   ISSN = {0033-3158},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/9725745},
   Keywords = {Acetylcholine • Animals • Attention •
             Cognition • Humans • Memory • Nicotinic
             Agonists • Receptors, Neurotransmitter •
             Receptors, Nicotinic • drug effects • metabolism*
             • pharmacology • physiology* • therapeutic
             use},
   Abstract = {Nicotinic cholinergic systems are involved with several
             important aspects of cognitive function including attention,
             learning and memory. Nicotinic cholinergic receptors are
             located in many regions of the brain, including areas
             important for cognitive function such as the hippocampus and
             frontal cortex. Nicotinic agonists have been found in rodent
             and non-human primate studies to improve performance on a
             variety of memory tasks. In a complementary fashion,
             nicotinic antagonists such as mecamylamine impair working
             memory function. In humans, similar effects have been seen.
             Nicotinic agonist treatment can improve attention, learning
             and memory and nicotinic antagonist treatment can cause
             deficits. To define the neural substrates of nicotinic
             involvement in cognitive function, three areas of
             investigation are underway. 1) Critical neuroanatomic loci
             for nicotinic effects are beginning to be determined. The
             hippocampus, frontal cortex and midbrain dopaminergic nuclei
             have been found to be important sites of action for
             nicotinic involvement in memory function. 2) Nicotinic
             receptor subtype involvement in cognitive function is being
             studied. There has been considerable recent work identifying
             nicotinic receptor subunit conformation including alpha and
             beta subunits. Nicotinic receptor subtypes appear to be
             associated with different functional systems; however, much
             remains to be done to determine the precise role each
             subtype plays in terms of cognitive function. 3) Nicotinic
             interactions with other transmitter systems are being
             assessed. Nicotine receptors interact in important ways with
             other systems to affect cognitive functioning, including
             muscarinic ACh, dopamine, norepinepherine, serotonin,
             glutamate, and other systems. Nicotinic function in clinical
             populations and potential for therapeutics has been
             investigated for Alzheimer's disease, Parkinson's disease,
             schizophrenia and attention deficit/hyperactivity disorder.
             Areas which need to receive greater attention are the exact
             anatomical location and the specific receptor subtypes
             critically involved in nicotine's effects. In addition, more
             work needs to be done to develop and determine the efficacy
             and safety of novel nicotinic ligands for use in the
             long-term treatment of human cognitive disorders.},
   Doi = {10.1007/s002130050667},
   Key = {fds274492}
}

@article{fds274442,
   Author = {Kelly, KA and Havrilla, CM and Brady, TC and Abramo, KH and Levin,
             ED},
   Title = {Oxidative stress in toxicology: established mammalian and
             emerging piscine model systems.},
   Journal = {Environmental Health Perspectives},
   Volume = {106},
   Number = {7},
   Pages = {375-384},
   Year = {1998},
   Month = {July},
   ISSN = {0091-6765},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/9637794},
   Keywords = {Animals • Antioxidants • Fishes • Humans
             • Mammals • Models, Biological • Oxidative
             Stress • Reactive Oxygen Species • Toxicology
             • drug effects* • metabolism • metabolism*
             • methods* • pharmacology},
   Abstract = {Interest in the toxicological aspects of oxidative stress
             has grown in recent years, and research has become
             increasingly focused on the mechanistic aspects of oxidative
             damage and cellular responses in biological systems. Toxic
             consequences of oxidative stress at the subcellular level
             include lipid peroxidation and oxidative damage to DNA and
             proteins. These effects are often used as end points in the
             study of oxidative stress. Typically, mammalian species have
             been used as models to study oxidative stress and to
             elucidate the mechanisms underlying cellular damage and
             response, largely because of the interest in human health
             issues surrounding oxidative stress. However, it is becoming
             apparent that oxidative stress also affects aquatic
             organisms exposed to environmental pollutants. Research in
             fish has demonstrated that mammalian and piscine systems
             exhibit similar toxicological and adaptive responses to
             oxidative stress. This suggests that piscine models, in
             addition to traditional mammalian models, may be useful for
             further understanding the mechanisms underlying the
             oxidative stress response.},
   Doi = {10.1289/ehp.98106375},
   Key = {fds274442}
}

@article{fds274391,
   Author = {Schwartz-Bloom, RD and McDonough, KJ and Chase, PJ and Chadwick, LE and Inglefield, JR and Levin, ED},
   Title = {Long-term neuroprotection by benzodiazepine full versus
             partial agonists after transient cerebral ischemia in the
             gerbil [corrected].},
   Journal = {Journal of Cerebral Blood Flow and Metabolism},
   Volume = {18},
   Number = {5},
   Pages = {548-558},
   Year = {1998},
   Month = {May},
   ISSN = {0271-678X},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/9591847},
   Keywords = {Animals • Benzodiazepines • Cell Death • GABA
             Modulators • Gerbillinae • Hypothermia, Induced
             • Imidazoles • Injections, Intraperitoneal •
             Ischemic Attack, Transient • Male • Time Factors
             • administration & dosage* • adverse effects
             • drug effects • drug therapy* •
             pathology*},
   Abstract = {The ability of diazepam, a benzodiazepine full agonist, and
             imidazenil, a benzodiazepine partial agonist, to protect
             hippocampal area CA1 neurons from death for at least 35 days
             after cerebral ischemia was investigated. Diazepam (10
             mg/kg) administered to gerbils 30 and 90 minutes after
             forebrain ischemia produced significant protection of
             hippocampal area CA1 pyramidal neurons 7 days later. In
             gerbils surviving for 35 days, diazepam produced the same
             degree of neuroprotection (70% +/- 30%) in the hippocampus
             compared with 7 days after ischemia. The therapeutic window
             for diazepam was short; there was no significant
             neuroprotection when the administration of diazepam was
             delayed to 4 hours after ischemia. The neuroprotective dose
             of diazepam also produced hypothermia (approximately 32
             degrees C) for several hours after injection. To assess the
             role of hypothermia in neuroprotection by diazepam,
             hypothermia depth and duration was simulated using a
             cold-water spray in separate gerbils. Seven days after
             ischemia, neuroprotection by hypothermia was similar to that
             produced by diazepam. However, 35 days after ischemia, there
             was no significant protection by hypothermia, suggesting
             that hypothermia does not play a significant role in
             long-term diazepam neuroprotection. Imidazenil (3 mg/kg),
             which produced only minimal hypothermia, protected area CA1
             of hippocampus to the same degree as that by diazepam 7 days
             after ischemia. At 35 days after ischemia, significant
             protection remained, but it was considerably reduced
             compared with 7 days. Like diazepam, the therapeutic window
             for imidazenil was short. Imidazenil neuroprotection was
             lost when the drug was administered as early as 2 hours
             after ischemia. The ability of ischemia to produce deficits
             in working memory and of benzodiazepines to prevent the
             deficits also was investigated. Gerbils trained on an
             eight-arm radial maze before ischemia demonstrated a
             significant increase in the number of working errors 1 month
             after ischemia. The ischemia-induced deficits in working
             memory were completely prevented by diazepam but not by
             imidazenil. There was a significant, but weak, negative
             correlation between the degree of CA1 pyramidal cell
             survival and the number of working errors in both the
             diazepam and imidazenil groups. Thus, if given early enough
             during reperfusion, both benzodiazepine full and partial
             agonists are neuroprotective for at least 35 days, but the
             lack of sedating side effects of imidazenil must be weighed
             against its reduced efficacy.},
   Doi = {10.1097/00004647-199805000-00010},
   Key = {fds274391}
}

@article{fds274381,
   Author = {Markwiese, BJ and Acheson, SK and Levin, ED and Wilson, WA and Swartzwelder, HS},
   Title = {Differential effects of ethanol on memory in adolescent and
             adult rats.},
   Journal = {Alcoholism, Clinical and Experimental Research},
   Volume = {22},
   Number = {2},
   Pages = {416-421},
   Year = {1998},
   Month = {April},
   ISSN = {0145-6008},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/9581648},
   Keywords = {Aging • Animals • Discrimination Learning •
             Dose-Response Relationship, Drug • Escape Reaction
             • Ethanol • Hippocampus • Injections,
             Intraperitoneal • Male • Maze Learning •
             Memory • Mental Recall • Neuronal Plasticity
             • Orientation • Rats • Rats, Sprague-Dawley
             • Synaptic Transmission • drug effects • drug
             effects* • toxicity*},
   Abstract = {Previous studies have shown that ethanol inhibits
             memory-related synaptic activity and plasticity more
             potently in hippocampal slices from immature rats, compared
             with those taken from adults. We therefore hypothesized that
             ethanol would more potently attenuate the acquisition of
             spatial memory in adolescents, compared with adult rats.
             Adult (65 days of age) and adolescent (30 days of age) male
             rats were given five daily trials on a spatial memory task
             in a Morris Water Maze. The animals from each age group were
             subdivided into three subgroups. Each day, thirty minutes
             before training, the animals in each subgroup were given an
             intraperitoneal injection of 1.0 g/kg of ethanol, 2.0 g/kg
             of ethanol, or the saline vehicle. Training continued daily
             until the control animals had reached a performance
             criterion. Ethanol treatment significantly impaired spatial
             memory acquisition in the adolescent rats, but did not
             impair acquisition in adult rats. A separate experiment with
             identical treatment groups showed that ethanol did not
             impair acquisition of a nonspatial memory task in the water
             maze in animals from either age group. These experiments
             show that the acquisition of spatial, but not nonspatial,
             memory is more potently impaired by ethanol in adolescent
             animals, compared with adults.},
   Doi = {10.1097/00000374-199804000-00018},
   Key = {fds274381}
}

@article{fds136380,
   Title = {Kelly SA, CM Havrilla, TC Brady, KL Harris amd ED Levin.
             Oxidative stress in toxicology: Established mammalian and
             emerging piscine model systems. Environmental Health
             Perspectives, 106:375-384, 1998.},
   Year = {1998},
   Key = {fds136380}
}

@article{fds136381,
   Title = {Levin ED and TA Slotkin. Developmental neurotoxicity of
             nicotine. In Handbook of Developmental Neurotoxicology, (W.
             Slikker, Jr. and L.W. Chang eds.), Academic Press, San
             Diego, pp. 587-615, 1998.},
   Year = {1998},
   Key = {fds136381}
}

@article{fds136382,
   Title = {Levin ED, CK Conners, D Silva, SC Hinton , WH Meck, J March
             and JE Rose. Transdermal nicotine effects on attention.
             Psychopharmacology, 140:135-141, 1998.},
   Year = {1998},
   Key = {fds136382}
}

@article{fds136397,
   Title = {Levin ED and BB Simon. Nicotinic acetylcholine involvement
             in cognitive function in animals. Psychopharmacology,
             138:217-230, 1998.},
   Year = {1998},
   Key = {fds136397}
}

@article{fds136398,
   Title = {Levin ED, BB Simon and CK Conners. Transdermal nicotine
             treatment of attention deficit/hyperactivity disorder. In:
             Neuronal Nicotinic Receptors: Pharmacology and Therapeutic
             Opportunities, S.P. Arneric and J.D. Brioni (eds.), John
             Wiley, New York,349-357, 1998.},
   Year = {1998},
   Key = {fds136398}
}

@article{fds136399,
   Title = {Levin ED, EC Hochrein, TC Brady, TD Oury, LM Jonsson, SL.
             Marklund and J. Crapo Molecular manipulations of
             extracellular superoxide dismutase: functional importance
             for learning. Behavior Genetics, 28:381-390,
             1998.},
   Year = {1998},
   Key = {fds136399}
}

@article{fds274356,
   Author = {Levin, ED and Schmechel, DE and Burkholder, JB and Deamer-Melia, NJ and Moser, VC and Harry, GJ},
   Title = {Persisting learning deficits in rats after exposure to
             Pfiesteria piscicida.},
   Journal = {Environmental Health Perspectives},
   Volume = {105},
   Number = {12},
   Pages = {1320-1325},
   Year = {1997},
   Month = {December},
   ISSN = {0091-6765},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/9405328},
   Keywords = {Animals • Dinoflagellida* • Female • Learning
             Disorders • Maze Learning • Motor Activity •
             Protozoan Infections, Animal • Rats • Rats,
             Sprague-Dawley • blood • complications* •
             etiology*},
   Abstract = {Pfiesteria piscicida and other toxic Pfiesteria-like
             dinoflagellates have been implicated as a cause of fish
             kills in North Carolina estuaries and elsewhere. Accidental
             laboratory exposure of humans to P. piscicida has been
             reported to cause a complex syndrome including cognitive
             impairment. The current project was conducted to
             experimentally assess the possibility of cognitive effects
             of P. piscicida exposure in rats. Samples of water from
             aquaria in which P. piscicida zoospores were killing fish
             were frozen, a procedure that has been found to induce
             encystment. Thawed samples were injected into albino
             Sprague-Dawley rats. A significant learning impairment was
             documented in rats administered samples of P. piscicida that
             were recently frozen. Prolonged storage of Pfiesteria
             samples diminished the effect. No effect was seen in the
             recall of a previously learned task, but when the rats were
             called upon to learn a new task, the Pfiesteria-treated
             animals showed a significant learning deficit. This effect
             persisted up to at least 10 weeks after a single injection
             of Pfiesteria. The Pfiesteria-induced learning deficit did
             not seem to be associated with any obvious debilitation or
             health impairment of the exposed rats. Deficits in
             habituation of arousal and rearing behavior were detected
             using a functional observational battery. No
             Pfiesteria-induced effects on blood count and white cell
             differential or in a standard pathological screening of
             brain, liver, lung, kidney, and spleen tissue were seen at 2
             months after exposure. These studies document a persistent
             learning impairment in rats after exposure to the
             dinoflagellate P.piscicida in otherwise physically
             well-appearing rats. This effect may partially model the
             symptoms of cognitive impairments that humans have shown
             after Pfiesteria exposure.},
   Doi = {10.1289/ehp.971051320},
   Key = {fds274356}
}

@article{fds274405,
   Author = {Levin, ED},
   Title = {Chronic haloperidol administration does not block acute
             nicotine-induced improvements in radial-arm maze performance
             in the rat.},
   Journal = {Pharmacology, Biochemistry, and Behavior},
   Volume = {58},
   Number = {4},
   Pages = {899-902},
   Year = {1997},
   Month = {December},
   ISSN = {0091-3057},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/9408193},
   Keywords = {Animals • Cholinergic Agents • Dopamine
             Antagonists • Dose-Response Relationship, Drug •
             Drug Implants • Female • Haloperidol • Maze
             Learning • Memory, Short-Term • Nicotine •
             Psychomotor Performance • Rats • Rats,
             Sprague-Dawley • administration & dosage •
             antagonists & inhibitors* • drug effects • drug
             effects* • pharmacology • pharmacology*},
   Abstract = {Nicotine has been found to improve cognitive performance in
             a variety of tasks including the radial maze. Nicotine has
             also been shown to promote the release of a variety of
             neurotransmitters including dopamine (DA). DA has been found
             to be important for nicotine's reinforcing effects. DA
             involvement with nicotine's cognitive effects is unclear. In
             the current study, the effects of acute nicotine injections
             (0, 0.1, 0.2, or 0.4 mg/kg) were examined on radial-arm maze
             performance in rats given chronic infusions the DA
             antagonist haloperidol (0, 0.2, or 0.6 mg/kg/day). Chronic
             haloperidol infusion was not found to attenuate the memory
             improvement caused by acute nicotine injection. In fact, the
             dose-related nicotine-induced memory improvement was clearer
             in the haloperidol-treated groups than in controls. This is
             similar to the effect of nicotine we saw in human subjects
             given chronic doses of haloperidol. Our previous studies
             demonstrated significant nicotinic-DA interactions with
             regard to memory function. The current results suggest that
             in the DA-nicotinic relationship DA stimulation is not
             necessary for the memory improvement caused by
             nicotine.},
   Doi = {10.1016/s0091-3057(97)00052-x},
   Key = {fds274405}
}

@article{fds274406,
   Author = {Felix, R and Levin, ED},
   Title = {Nicotinic antagonist administration into the ventral
             hippocampus and spatial working memory in
             rats.},
   Journal = {Neuroscience},
   Volume = {81},
   Number = {4},
   Pages = {1009-1017},
   Year = {1997},
   Month = {December},
   ISSN = {0306-4522},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/9330363},
   Keywords = {Aconitine • Animals • Cholinergic Antagonists
             • Dihydro-beta-Erythroidine • Female •
             Hippocampus • Maze Learning • Memory, Short-Term
             • Neuromuscular Blocking Agents • Nicotinic
             Antagonists • Rats • Rats, Sprague-Dawley •
             Seizures • Space Perception • Tubocurarine •
             administration & dosage • analogs & derivatives •
             chemically induced • drug effects • drug effects*
             • pharmacology • pharmacology*},
   Abstract = {Nicotinic acetylcholine receptors are important for
             maintaining optimal memory performance. In order to more
             fully characterize the involvement of nicotinic systems in
             memory, the contributions of nicotinic acetylcholine
             receptor subtypes were investigated. This study targeted the
             alpha 7 and alpha 4 beta 2 nicotinic receptors in the
             ventral hippocampus, an area known to be important for
             spatial working memory. Antagonists of alpha 7 and alpha 4
             beta 2 receptors were locally infused into the ventral
             hippocampus of rats and the effects on memory were examined
             with the radial-arm maze. The subtype-specific competitive
             antagonists infused into separate groups of rats were
             methyllycaconitine citrate (an alpha 7 antagonist) and
             dihydro-beta-erythroidine hydrobromide (an alpha 4 beta 2
             antagonist). Their effects on radial-arm maze performance
             were contrasted with the non-specific competitive
             antagonist, D-tubocurarine chloride. Significant deficits in
             radial-arm maze choice accuracy performance were found at
             78.7 micrograms/side for methyllycaconitine and at 106.9
             micrograms/side for dihydro-beta-erythroidine. Increased
             response latency was also seen at these doses. Tubocurarine
             induced seizures at doses previously reported to have no
             effect. Wet dog shakes were seen in most rats at 0.1
             microgram/side with tubocurarine, 26.3 micrograms/side with
             methyllycaconitine and 106.9 micrograms/side with
             dihydro-beta-erythroidine. This study suggests that both
             alpha 7 and alpha 4 beta 2 nicotinic acetylcholine receptor
             subtypes are involved in working memory formation and that
             the hippocampus is a critical site for nicotinic cholinergic
             involvement in memory function, though the high doses of
             antagonists needed to produce the memory impairment may have
             had less than completely specific effects.},
   Doi = {10.1016/s0306-4522(97)00224-8},
   Key = {fds274406}
}

@article{fds274410,
   Author = {Piantadosi, CA and Zhang, J and Levin, ED and Folz, RJ and Schmechel,
             DE},
   Title = {Apoptosis and delayed neuronal damage after carbon monoxide
             poisoning in the rat.},
   Journal = {Experimental Neurology},
   Volume = {147},
   Number = {1},
   Pages = {103-114},
   Year = {1997},
   Month = {September},
   ISSN = {0014-4886},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/9294407},
   Keywords = {Animals • Apoptosis • Behavior, Animal •
             Brain • Carbon Monoxide Poisoning • DNA
             Fragmentation • Glutamic Acid • Hydroxyl Radical
             • Hydroxylation • Male • Microdialysis •
             Microscopy, Electron • Neurons • Rats • Rats,
             Sprague-Dawley • Time Factors • drug effects
             • drug effects* • genetics • metabolism
             • pathology • pathology* • physiology •
             psychology • ultrastructure},
   Abstract = {Delayed neurological damage after CO hypoxia was studied in
             rats to determine whether programmed cell death (PCD), in
             addition to necrosis, is involved in neuronal death. In rats
             exposed to either air or CO (2500 ppm), microdialysis in
             brain cortex and hippocampus was performed to determine the
             extent of glutamate release and hydroxyl radical generation
             during the exposures. Groups of control and CO-exposed rats
             also were tested in a radial maze to assess the effects of
             the CO exposures on learning and memory. At 3, 7, and 21
             days after CO exposure brains were perfusion-fixed and
             hematoxylin-eosin (H&E) was used to assess injury and to
             select regions for further examination. DNA fragmentation
             was sought by examining cryosections with the terminal
             deoxynucleotidyl transferase-mediated dUTP-biotin nick-end
             labeling (TUNEL) reaction. We found significant increases in
             glutamate release and .OH generation during and immediately
             after CO hypoxia. CO-exposed rats showed learning and memory
             deficits after exposure associated with heterogeneous cell
             loss in cortex, globus pallidus, and cerebellum. The frontal
             cortex was affected most seriously; the damage was slight at
             Day 3, increased at Day 7, and persistent at Day 21 after CO
             exposure. TUNEL staining was positive at all three time
             points, and TUNEL-labeled cells were distributed similarly
             to eosinophilic cells. The number of cells stained by TUNEL
             was less than by H&E and amounted to 2 to 5% of all cell
             nuclei in regions of injury. Ultrastructural features of
             both neuronal necrosis and apoptosis also were observed
             readily by electron microscopy. These findings indicate that
             both necrosis and apoptosis (PCD) contribute to CO
             poisoning-induced brain cell death.},
   Doi = {10.1006/exnr.1997.6584},
   Key = {fds274410}
}

@article{fds274446,
   Author = {Newhouse, PA and Potter, A and Levin, ED},
   Title = {Nicotinic system involvement in Alzheimer's and Parkinson's
             diseases. Implications for therapeutics.},
   Journal = {Drugs & Aging},
   Volume = {11},
   Number = {3},
   Pages = {206-228},
   Year = {1997},
   Month = {September},
   ISSN = {1170-229X},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/9303280},
   Keywords = {Alzheimer Disease • Animals • Cognition •
             Cognition Disorders • Combined Modality Therapy •
             Disease Models, Animal • Humans • Nicotine •
             Nicotinic Agonists • Nicotinic Antagonists •
             Parkinson Disease • Receptors, Nicotinic • drug
             effects • drug therapy • etiology •
             metabolism • metabolism* • pharmacology •
             therapeutic use*},
   Abstract = {Advances in our understanding of the structure, function and
             distribution of nicotinic acetylcholine receptors in the CNS
             have provided the impetus for new studies examining the
             role(s) that these receptors and associated processes may
             play in CNS functions. Further motivation has come from the
             realisation that such receptors must be involved in the
             maintenance of cigarette smoking, and from clues provided by
             studies of degenerative neurological diseases such as
             Alzheimer's disease and Parkinson's disease, in which the
             loss of nicotinic receptors has been described. Ongoing
             investigations of the molecular substructure of central
             nicotinic receptors and their pharmacology have begun to
             open up new possibilities for novel CNS therapeutics with
             nicotinic agents. Exploiting these possibilities will
             require understanding of the role(s) that these receptor
             systems play in human cognitive, behavioural, motor and
             sensory functioning. Clues from careful studies of human
             cognition are beginning to emerge and will provide direction
             for studies of potentially therapeutic novel nicotinic
             agents. Despite the promising results of acute studies, few
             long term studies with nicotine or nicotinic drugs have been
             performed in dementing disorders. Thus there is uncertainty
             as to whether long term nicotinic treatment will provide
             sustained cognitive benefit. It is even more uncertain
             whether such cognitive benefit will have a significant
             clinical impact on patients and their families. To maximise
             the potential benefit of long term treatment with nicotinic
             agonists (or other cholinergic drugs), we suggest that drug
             treatment should be combined with cognitive rehabilitation
             strategies. This will enable patients and/or their families
             to focus on the particular cognitive domains that may be
             improved.},
   Doi = {10.2165/00002512-199711030-00005},
   Key = {fds274446}
}

@article{fds274432,
   Author = {Levin, ED and Kaplan, S and Boardman, A},
   Title = {Acute nicotine interactions with nicotinic and muscarinic
             antagonists: working and reference memory effects in the
             16-arm radial maze.},
   Journal = {Behavioural Pharmacology},
   Volume = {8},
   Number = {2-3},
   Pages = {236-242},
   Year = {1997},
   Month = {June},
   ISSN = {0955-8810},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/9833018},
   Keywords = {Animals • Drug Interactions • Female • Maze
             Learning • Mecamylamine • Memory, Short-Term
             • Muscarinic Antagonists • Nicotine •
             Nicotinic Agonists • Nicotinic Antagonists • Rats
             • Rats, Sprague-Dawley • Scopolamine • drug
             effects* • pharmacology • pharmacology*},
   Abstract = {In the 8-arm radial maze and other tests, acute nicotine
             administration has been found to improve memory performance
             significantly, whereas acute administration of the nicotinic
             antagonist mecamylamine has been found to impair memory
             performance. However, questions remain concerning the
             behavioral and pharmacological nature of acute nicotine
             effects on memory. In the current studies, we examined acute
             nicotine effects on working and reference memory in a 16-arm
             radial maze. In the first study, nicotine caused a
             significant improvement in working memory but not in
             reference memory. The muscarinic antagonist scopolamine
             caused significant deficits in working memory but not in
             reference memory. Nicotine did not significantly attenuate
             the scopolamine-induced deficit. In the second study, with
             rats trained to near-perfect performance, a low dose of
             mecamylamine (1.25 mg/kg) caused a significant working
             memory impairment in the 16-arm maze. This deficit was
             significantly attenuated by concurrent acute administration
             of nicotine. These studies show that acute nicotine, like
             chronic nicotine, preferentially improves working compared
             with reference memory in the radial-arm maze. Mecamylamine
             can impair working memory performance in the 16-arm maze at
             low doses which are less likely to have effects at
             N-methyl-D-aspartate receptors. Nicotine can selectively
             reverse mecamylamine-induced deficits.},
   Key = {fds274432}
}

@article{fds274434,
   Author = {Levin, ED and Christopher, NC and Briggs, SJ},
   Title = {Chronic nicotinic agonist and antagonist effects on T-maze
             alternation.},
   Journal = {Physiology & Behavior},
   Volume = {61},
   Number = {6},
   Pages = {863-866},
   Year = {1997},
   Month = {June},
   ISSN = {0031-9384},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/9177558},
   Keywords = {Animals • Female • Maze Learning •
             Mecamylamine • Nicotine • Rats • Rats,
             Sprague-Dawley • Time Factors • drug effects*
             • pharmacology*},
   Abstract = {A variety of studies have found that nicotine improves
             working memory function. However, other studies have either
             not found improvements or have found nicotine-induced
             deficits. The demands of the particular memory test may be
             critical for the expression of the nicotine effects. In
             several studies, we have found that chronic nicotine
             administration improves working memory performance in the
             radial arm maze. Chronic mecamylamine coadministration
             reversed this effect. The current study was conducted to
             determine the effects of chronic nicotine and mecamylamine
             on choice accuracy in a T-maze spatial alternation task. The
             same dose and duration of nicotine administration that we
             have previously found to significantly improve choice
             accuracy in the radial-arm maze was not effective in
             altering T-maze spatial alternation. The critical difference
             in task demands may be the presence with T-maze alternation
             of proactive interference. During a session, a choice
             alternative repeatedly changes valence from correct to
             incorrect and back again. In contrast, with the radial-arm
             maze as run in our studies, in a session the valence of an
             arm only changes once from correct to incorrect. Previous
             work with nicotine effects on spatial alternation in an
             operant task found evidence that nicotine increased the
             negative effect of proactive interference on performance. In
             the current study, chronic mecamylamine caused a significant
             deficit in T-maze spatial alternation. This same dose did
             not produce a deficit in the radial-arm maze and, in fact,
             caused an improvement during the first week of
             administration.},
   Doi = {10.1016/s0031-9384(96)00609-9},
   Key = {fds274434}
}

@article{fds136374,
   Title = {Levin ED, DE Schmechel, JM Burkholder, HB Glasgow, Jr., N
             Deamer-Melia, VC Moser and G.J. Harry. Persisting learning
             deficits in rats after exposure to pfiesteria piscicida.
             Environmental Health Perspectives, 105:1320-1325,
             1997.},
   Year = {1997},
   Key = {fds136374}
}

@article{fds136379,
   Title = {Levin ED, D Torry, NC Christopher, X Yu, G Einstein and R
             Schwartz-Bloom. Is binding to nicotinic acetylcholine and
             dopamine receptors related to working memory in rats?. Brain
             Research Bulletin, 43:295-304, 1997.},
   Year = {1997},
   Key = {fds136379}
}

@article{fds136396,
   Title = {Levin ED, NC Christopher and SJ Briggs. Chronic nicotinic
             agonist and antagonist effects on T-maze alternation.
             Physiology and Behavior, 61:863-866, 1997.},
   Year = {1997},
   Key = {fds136396}
}

@article{fds274385,
   Author = {Levin, ED and Torry, D and Christopher, NC and Yu, X and Einstein, G and Schwartz-Bloom, RD},
   Title = {Is binding to nicotinic acetylcholine and dopamine receptors
             related to working memory in rats?},
   Journal = {Brain Research Bulletin},
   Volume = {43},
   Number = {3},
   Pages = {295-304},
   Year = {1997},
   ISSN = {0361-9230},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/9227840},
   Keywords = {Animals • Dose-Response Relationship, Drug • Maze
             Learning • Mecamylamine • Memory • Nicotine
             • Radioligand Assay • Rats • Rats,
             Sprague-Dawley • Receptors, Dopamine • Receptors,
             Nicotinic • drug effects • drug effects* •
             pharmacology* • physiology*},
   Abstract = {Nicotinic acetylcholine (ACh) and dopamine (DA) receptor
             activation has been found to be important for working
             memory. The regional distribution of these receptors in the
             brain has been well characterized. However, the relationship
             of the region-specific nicotinic ACh and DA binding density
             to memory performance has not been well assessed. In the
             current studies the relationship of receptor binding and
             memory function was examined. Receptor binding and memory
             performance were assessed in rats in three types of
             conditions: 1) chronic nicotine and mecamylamine vs. vehicle
             infusion; 2) lesions of the fimbria-fornix or medial
             basalocortical projection vs. sham lesions; and 3)
             2-year-old aged rats vs. 3-month-old young adult rats.
             Nicotinic ACh receptors were labeled by [3H]N-methyl-carbamylcholine
             ([3H]MCC), D1 receptors by [3H]SCH 23390, and D2 receptors
             by [125I]iodosulpiride. Working memory was assessed using
             the radial-arm maze and T-maze delayed spatial alternation
             tasks. Chronic nicotine infusion substantially increased
             nicotinic receptor binding in a variety of brain areas and
             significantly improved working memory performance in the
             radial-arm maze. However, nicotinic receptor binding did not
             correlate well with memory performance. The nicotinic
             antagonist mecamylamine did not block nicotine-induced
             increased nicotinic binding, but it did block
             nicotine-induced memory improvement. Aged rats relative to
             young adults showed both a decrease in nicotinic binding and
             impaired memory performance. However, chronic effects of
             nicotine on nicotinic receptor binding and memory
             performance did not correlate in the aged rats. Nicotine
             also increased nicotinic receptor binding in the aged rats
             in brain areas except for the VTA, but did not improve
             memory performance. Lesions of the medial basalocortical
             projection or the fimbria-fornix did not cause significant
             changes in nicotinic binding in their target fields, but
             they did cause significant deficits in memory performance.
             Finally, there were no significant correlations of nicotinic
             binding in any brain region and memory performance. DA
             receptor binding was not altered by chronic nicotine or
             mecamylamine infusion, fimbria-fornix lesions, medial
             basalocortical lesions, or in aged rats. However, DA
             receptor binding did correlate with memory performance.
             There was a positive correlation of T-maze accuracy and D1
             receptor binding in the frontal cortex and a negative
             correlation of T-maze accuracy and D1 receptor binding in
             the VTA and dentate gyrus. In contrast, a positive
             correlation was seen between radial-arm maze accuracy and D1
             receptor binding in the VTA. Radial-arm maze accuracy was
             positively correlated with D2 receptor binding in the
             striatum and dentate gyrus. There are significant
             relationships between the extent of DA receptor binding and
             working memory, but relationship between nicotinic ACh
             receptor binding density and memory is weak.},
   Doi = {10.1016/s0361-9230(97)00009-9},
   Key = {fds274385}
}

@article{fds274345,
   Author = {Levin, ED and Wilkerson, A and Jones, JP and Christopher, NC and Briggs,
             SJ},
   Title = {Prenatal nicotine effects on memory in rats: pharmacological
             and behavioral challenges.},
   Journal = {Brain Research. Developmental Brain Research},
   Volume = {97},
   Number = {2},
   Pages = {207-215},
   Year = {1996},
   Month = {December},
   ISSN = {0165-3806},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/8997505},
   Keywords = {Animals • Drug Evaluation, Preclinical • Female
             • Infusion Pumps • Male • Maze Learning
             • Memory Disorders • Nicotine • Nicotinic
             Agonists • Osmotic Pressure • Pregnancy •
             Prenatal Exposure Delayed Effects* • Rats • Rats,
             Sprague-Dawley • Receptors, Adrenergic • Sex
             Distribution • chemically induced* • drug effects
             • drug effects* • pharmacology* • physiology*
             • physiopathology},
   Abstract = {Cigarette smoking during pregnancy has been shown in a
             variety of studies to be associated with cognitive deficits
             in the children. Nicotine administration to rats during
             gestation has been found to cause subtle cognitive effects
             in the offspring. Some individual differences in cognitive
             impairment may be related to prenatal nicotine effects on
             noradrenergic (NE) systems. In the current study, 10
             Sprague-Dawley rat dams were infused with approximately 2
             mg/kg/day of nicotine ditartrate via osmotic minipumps and
             10 control dams were exposed to vehicle-containing minipumps
             from gestational day (GD) 4-20. Starting on postnatal day
             (PND) 50, the offspring were tested for T-maze rewarded
             spatial alternation with intertrial intervals of 0, 10, 20,
             or 40 s. There was a sex- and delay-dependent effect of
             prenatal nicotine exposure on T-maze alternation.
             Nicotine-exposed males showed a significant deficit at the 0
             s delay. In radial-arm maze (RAM) acquisition training there
             were no significant nicotine effects. However, significant
             nicotine-related effects were seen with subsequent
             behavioral and pharmacological challenges in the RAM.
             Changing the RAM testing location to an identical maze in a
             different room elicited a significant choice accuracy
             deficit in the prenatal nicotine-exposed rats compared with
             controls. Acute nicotine challenge did not cause any
             differential effects in the prenatal nicotine and control
             groups. During the isoproterenol (beta-NE agonist) challenge
             phase there appeared a significant facilitation of choice
             accuracy and speeding of response in the prenatal nicotine
             exposure group which was not seen in the control group. The
             alpha-NE agonist phenylpropanolamine caused a significant
             deficit in control females but not in the females prenatally
             exposed to nicotine. No differential effects of the alpha-NE
             antagonist phenoxybenzamine were seen in the prenatal
             nicotine and control groups. Throughout RAM testing there
             was a significant sex effect with males having better choice
             accuracy than females. These results demonstrate that the
             persisting cognitive effects of prenatal exposure to 2
             mg/kg/day cause subtle effects in cognitive performance
             which can be elicited with behavioral and pharmacological
             challenge. These results also support previous studies
             suggesting the involvement of NE systems in persisting
             effects of prenatal nicotine exposure.},
   Doi = {10.1016/s0165-3806(96)00144-7},
   Key = {fds274345}
}

@article{fds274211,
   Author = {Levin, ED and Rose, JE and Lippelio, P and Robinson,
             J},
   Title = {Nicotine and neurobehavioral function},
   Journal = {Drug Development Research},
   Volume = {38},
   Number = {3-4},
   Pages = {135},
   Publisher = {WILEY},
   Year = {1996},
   Month = {December},
   ISSN = {0272-4391},
   url = {http://dx.doi.org/10.1002/(SICI)1098-2299(199607/08)38:3/4<135::AID-DDR1>3.0.C},
   Doi = {10.1002/(SICI)1098-2299(199607/08)38:3/4<135::AID-DDR1>3.0.C},
   Key = {fds274211}
}

@article{fds274335,
   Author = {Levin, ED and Toll, K and Chang, G and Christopher, NC and Briggs, SJ and Fiedler, W},
   Title = {Epibatidine, a potent nicotinic agonist: Effects on learning
             and memory in the radial-arm maze},
   Journal = {Medicinal Chemistry Research},
   Volume = {6},
   Number = {7-8},
   Pages = {543-554},
   Year = {1996},
   Month = {December},
   Abstract = {Epibatidine is a potent nicotinic agonist originally
             isolated from frog skin. Nicotine has been found in a
             variety of studies to improve working memory function in
             several different tests including the radial-arm maze (RAM).
             The current studies were conducted to determine if
             epibatidine would affect learning and memory in the
             radial-arm maze. Three studies were conducted. In the first
             study, rats were pretrained on the radial-arm maze and then
             given acute doses of epibatidine (0, 0.25, 0.5 and 1.0
             μg/kg) in a repeated measures counter-balanced design.
             Compared to memory performance either before or after the
             drug study, performance during the drug study was
             significantly improved. This was true even with the
             intercurrent saline injections. This may have resulted from
             persisting effects of epibatidine administration. Because of
             this possibility of carryover effects the other studies both
             used between subjects designs. In the second study the rats
             were given 0, 0.5 or 1.0 μg/kg of epibatidine in a between
             subjects design throughout 24 sessions of RAM training. The
             rats given 0.5 μg/kg had a trend toward improved choice
             accuracy performance relative to control during the middle
             phase of learning. The higher dose had no apparent effect.
             To determine if the transience of the improvement caused by
             0.5 μg/kg of epibatidine was due to the chronicity of the
             treatment or the phase of training a third study was
             conducted in which rats were pretrained for 12 sessions and
             then were given 0.5 μg/kg of epibatidine in a between
             subjects design for an additional 24 sessions of training.
             In this study when epibatidine was only given during the
             later phases of training no improvement was seen. In fact, a
             significant epibatidine deficit was seen during the final
             phase of training. These studies show that the potent
             nicotinic agonist epibatidine can significantly impair
             choice accuracy performance in the radial-arm maze. The
             expression of its effect depends critically on when during
             training it is given.},
   Key = {fds274335}
}

@article{fds274336,
   Author = {Levin, ED and Christopher, NC and Briggs, SJ and Todd Auman,
             J},
   Title = {Chronic nicotine-induced improvement of spatial working
             memory and D2 dopamine effects in
             rats},
   Journal = {Drug Development Research},
   Volume = {39},
   Number = {1},
   Pages = {29-35},
   Publisher = {WILEY},
   Year = {1996},
   Month = {December},
   url = {http://dx.doi.org/10.1002/(SICI)1098-2299(19960901)39:1<29::AID-DDR4>3.0.CO;2-},
   Abstract = {Nicotine improves working memory function in a variety of
             different testing situations. In a series of studies, we
             have found that chronic nicotine infusion improves working
             memory performance of rats in the win-shift version of the
             radial-arm maze. In the current studies, we examined the
             interaction of chronic nicotine effects in the radial-arm
             maze with dopamine D2 agonist and antagonist drugs, since we
             have previously found significant interactions of acute
             nicotinic agonist and antagonist effects with D2 systems.
             Replicating our earlier results, significant
             nicotine-induced improvements in working memory performance
             were seen. Chronic co-infusion of raclopride, a D2
             antagonist, or quinpirole, D2/D3 agonist, were not found to
             significantly interact with the choice accuracy improvement
             caused by nicotine. Acute challenge with a range of
             quinpirole doses also did not affect the facilitating effect
             of chronic nicotine. This stands in contrast to the
             significant interactions of D2 systems with acute nicotine
             effects. Acute and chronic nicotine administration have
             similar effects of facilitating memory performance in the
             radial-arm maze. However, these effects appear to have
             differential interactions with D2 systems.},
   Doi = {10.1002/(SICI)1098-2299(19960901)39:1<29::AID-DDR4>3.0.CO;2-},
   Key = {fds274336}
}

@article{fds274337,
   Author = {Levin, ED},
   Title = {Nicotinic agonist and antagonist effects on
             memory},
   Journal = {Drug Development Research},
   Volume = {38},
   Number = {3-4},
   Pages = {188-195},
   Publisher = {WILEY},
   Year = {1996},
   Month = {December},
   ISSN = {0272-4391},
   url = {http://dx.doi.org/10.1002/(SICI)1098-2299(199607/08)38:3/4<188::AID-DDR7>3.0.C},
   Abstract = {Nicotine has been found by a variety of investigators to
             improve memory in rats, monkeys, and humans. Recent studies
             have helped to determine the behavioral and pharmacological
             nature of critical nicotine effects on memory function.
             Other nicotinic agonists, including ABT-418, GTS-21, or
             lobeline, can also significantly improve memory performance.
             Conversely, nicotinic antagonists, such as mecamylamine, can
             impair memory. Nicotine can reverse memory impairments
             caused by aging or by lesions to hippocampal connections.
             The observation that nicotine improves memory performance
             when it is administered by chronic infusion is potentially
             important for the development of treatments of cognitive
             impairment. Nicotinic agonists show promise for the
             development of novel treatments for cognitive disorders.
             Some characteristics of nicotine, nicotinic receptors, and
             the nature of the disorders to be treated, however, present
             challenges to the development of nicotinic-based
             treatments.},
   Doi = {10.1002/(SICI)1098-2299(199607/08)38:3/4<188::AID-DDR7>3.0.C},
   Key = {fds274337}
}

@article{fds274387,
   Author = {Chambers, RA and Moore, J and McEvoy, JP and Levin,
             ED},
   Title = {Cognitive effects of neonatal hippocampal lesions in a rat
             model of schizophrenia.},
   Journal = {Neuropsychopharmacology},
   Volume = {15},
   Number = {6},
   Pages = {587-594},
   Year = {1996},
   Month = {December},
   ISSN = {0893-133X},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/8946433},
   Keywords = {Amphetamine • Animals • Behavior, Animal •
             Brain Diseases • Central Nervous System Stimulants
             • Disease Models, Animal • Female •
             Hippocampus • Ibotenic Acid • Male • Maze
             Learning* • Mecamylamine • Memory* •
             Muscarinic Antagonists • Nicotine • Nicotinic
             Agonists • Nicotinic Antagonists • Random
             Allocation • Rats • Rats, Sprague-Dawley •
             Schizophrenia • Schizophrenic Psychology •
             Scopolamine • chemically induced • drug effects
             • pathology* • pharmacology •
             psychology*},
   Abstract = {Lesioning the ventral hippocampus of neonatal rats has been
             proposed as an experimental model of schizophrenia. This
             lesion causes a syndrome of hyperresponsivity to the
             stimulant effects of amphetamine, impaired grooming and
             disrupted social interactions, effects that emerge during
             adolescence, much like schizophrenia. Persisting cognitive
             effects of neonatal ventral hippocampal lesions were
             assessed in the current study, because the hippocampus is
             critically important for a variety of cognitive functions
             and cognitive impairment and because it is an important
             feature of schizophrenia. Spatial learning and working
             memory were assessed in the radial-arm maze, which is
             sensitive to the adverse effects of hippocampal lesions made
             in adults. Lesioned rats showed pronounced deficits in
             radial-arm maze choice accuracy that persisted throughout
             training. Deficits were seen during the prepubertal period
             as well as in adulthood. Even though the lesioned rats
             performed more poorly, they were significantly less
             sensitive to the amnestic effects of the nicotinic
             antagonist mecamylamine and the muscarinic antagonist
             scopolamine. No significant effects of nicotine or
             amphetamine were seen in either the lesioned or control
             groups. The long-lasting deficits in spatial learning and
             working memory resulting from neonatal ventral hippocampal
             lesions show that, unlike frontal cortical lesions during
             the same age, the effects of hippocampal lesions are not
             overcome during development. The resistance to the amnestic
             effects of nicotinic and muscarinic acetylcholine (ACh)
             antagonists suggests that the hippocampus is a critical site
             for the action of these drugs. Neonatal hippocampal lesions
             may provide a good model of the cognitive impairments of
             schizophrenia and may be useful to assess novel drug effects
             to counteract the cognitive deficits in schizophrenia.},
   Doi = {10.1016/S0893-133X(96)00132-7},
   Key = {fds274387}
}

@article{fds274372,
   Author = {Levin, ED and Wilson, W and Rose, JE and McEvoy, J},
   Title = {Nicotine-haloperidol interactions and cognitive performance
             in schizophrenics.},
   Journal = {Neuropsychopharmacology},
   Volume = {15},
   Number = {5},
   Pages = {429-436},
   Year = {1996},
   Month = {November},
   ISSN = {0893-133X},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/8914115},
   Keywords = {Adult • Antipsychotic Agents • Cognition •
             Drug Synergism • Female • Haloperidol •
             Humans • Male • Memory • Middle Aged •
             Nicotine • Nicotinic Agonists • Reaction Time
             • Schizophrenia • drug effects • drug
             effects* • drug therapy* • therapeutic
             use*},
   Abstract = {Nearly 90% of schizophrenics smoke cigarettes, considerably
             higher than the general population's rate of 25%. There is
             some indication that schizophrenics may smoke as a form of
             self-medication. Nicotine has a variety of pharmacologic
             effects that may both counteract some of the cognitive
             deficits of schizophrenia and counteract some of the adverse
             side effects of antipsychotic drugs. In the current study,
             we assessed the interactions of haloperidol and nicotine on
             cognitive performance of a group of schizophrenics. These
             patients were in a double-blind study, randomly assigning
             them to low, moderate, and high dose levels of haloperidol.
             The subjects, all smokers, came to the laboratory on four
             different mornings after overnight deprivation from
             cigarettes. In a double-blind fashion, they were
             administered placebo, low (7 mg/day), medium (14 mg/day), or
             high (21 mg/day) dose nicotine skin patches. Three hours
             after administration of the skin patch, the subjects were
             given a computerized cognitive test battery including:
             simple reaction time, complex reaction time (spatial
             rotation), delayed matching to sample, the Sternberg memory
             test, and the Conners continuous performance test (CPT).
             With the placebo nicotine patch, there was a haloperidol
             dose-related impairment in delayed matching to sample choice
             accuracy and an increase in response time on the complex
             reaction time task. Nicotine caused a dose-related reversal
             of the haloperidol-induced impairments in memory performance
             and complex reaction time. In the CPT, nicotine reduced the
             variability in response that is associated with attentional
             deficit. These results demonstrate the effects of nicotine
             in reversing some of the adverse side effects of haloperidol
             and improving cognitive performance in schizophrenia.},
   Doi = {10.1016/S0893-133X(96)00018-8},
   Key = {fds274372}
}

@article{fds274497,
   Author = {Cutler, AR and Wilkerson, AE and Gingras, JL and Levin,
             ED},
   Title = {Prenatal cocaine and/or nicotine exposure in rats:
             preliminary findings on long-term cognitive outcome and
             genital development at birth.},
   Journal = {Neurotoxicology and Teratology},
   Volume = {18},
   Number = {6},
   Pages = {635-643},
   Year = {1996},
   Month = {November},
   ISSN = {0892-0362},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/8947940},
   Keywords = {Abnormalities, Drug-Induced* • Aging • Anal Canal
             • Analysis of Variance • Animals • Birth
             Weight • Cocaine • Cognition • Female •
             Litter Size • Male • Maze Learning • Memory
             • Nicotine • Penis • Pregnancy •
             Prenatal Exposure Delayed Effects* • Propranolol •
             Rats • Sex Differentiation • Sex Ratio •
             Sexual Maturation • Teratogens • Vagina •
             anatomy & histology • drug effects • drug effects*
             • pharmacology • toxicity •
             toxicity*},
   Abstract = {Prenatal cocaine or nicotine exposure is associated with a
             variety of teratogenic effects. The current study was
             conducted to determine their effects alone and in
             combination on cognitive function and sexual
             differentiation. Pregnant Long-Evans rats (N = 19) were
             exposed to either cocaine (15 mg/kg/dose b.i.d. SC on GD
             8-20); nicotine (4 mg/kg/day continuous SC infusion on GD
             4-20); both nicotine + cocaine; or vehicle only. Birth
             weight and anogenital distance (AGD) were measured in all
             pups at birth. Learning and memory were tested in the Morris
             water maze (MWM) during prepubertal and pubertal ages in
             five daily consecutive sessions and a sixth session 1 week
             later and in the radial-arm maze (RAM) during adulthood. In
             the RAM, a drug challenge of the beta-noradrenergic
             antagonist propranolol (10-20 mg/kg) was given after
             acquisition training. Maternal weight gain was reduced
             13-42% and offspring birth weight was reduced by 7-12% in
             all three exposure groups compared to controls. Cocaine
             decreased the AGD of males (2.68 mm) compared to 2.88 mm in
             noncocaine-exposed male pups (p < 0.025). A sex-selective
             cocaine effect was also seen after adjustment of AGD
             measurements for body weight. With this measure
             cocaine-treated females showed significantly (p < 0.05)
             greater AGD than those not exposed to cocaine. In the MWM,
             there were two types of trials: cued reference memory trials
             and uncued spatial working memory trials. On cued reference
             memory trials significant cocaine-induced latency deficits
             were seen on only the first session. On spatial working
             memory trials cocaine-induced latency deficits were seen
             throughout daily training on sessions 1-5, but not the
             retention session 6, 1 week later. During RAM acquisition,
             there were no significant differences in choice accuracy
             between exposure groups. Following propranolol challenge,
             deficits in choice accuracy were demonstrated in rats
             prenatally exposed to cocaine or nicotine. These rats did
             not show any response to propranolol, whereas the controls
             slightly improved their choice accuracy. The results of this
             study indicated that prenatal cocaine exposure altered
             long-term cognitive function under basal conditions in the
             MWM and drug challenge in the RAM, birth weight, and genital
             development. Cocaine-induced cognitive deficits were
             predominately in working memory rather than reference memory
             or long-term retention. Prenatal nicotine exposure was only
             observed to alter birth weight and cognitive function in
             response to propranolol challenge in the
             RAM.},
   Doi = {10.1016/s0892-0362(96)00125-0},
   Key = {fds274497}
}

@article{fds274418,
   Author = {Brucato, FH and Levin, ED and Mott, DD and Lewis, DV and Wilson, WA and Swartzwelder, HS},
   Title = {Hippocampal long-term potentiation and spatial learning in
             the rat: effects of GABAB receptor blockade.},
   Journal = {Neuroscience},
   Volume = {74},
   Number = {2},
   Pages = {331-339},
   Year = {1996},
   Month = {September},
   ISSN = {0306-4522},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/8865186},
   Keywords = {Animals • Behavior, Animal • Female • GABA
             Antagonists • Hippocampus • Learning •
             Long-Term Potentiation • Memory • Phosphinic Acids
             • Rats • Rats, Sprague-Dawley • Receptors,
             GABA-B • drug effects • drug effects* •
             pharmacology* • physiology*},
   Abstract = {This series of experiments assessed the role of GABAB
             receptors in the induction of long-term potentiation in the
             dentate gyrus in vivo, and spatial learning and memory in
             three different tasks. In urethane-anesthetized rats, the
             GABAB receptor antagonist CGP 46381 was injected
             intraperitoneally at a dose which effectively suppressed
             GABAB-mediated paired pulse disinhibition. Theta-burst
             stimulation reliably produced long-term potentiation in
             control rats. However, GABAB receptor blockade significantly
             suppressed the induction of long-term potentiation in the
             dentate gyrus. To compare the results of the long-term
             potentiation experiments with behavior, we assessed the
             performance of rats on several spatial learning and memory
             tasks in the presence of CGP 46381. We found that the
             working memory performance of highly trained rats on the
             eight-arm radial maze was unaffected by CGP 46381. There was
             also no effect of GABAB receptor blockade on learning in the
             eight-arm maze using a five-trial repeated acquisition
             paradigm. However, when we tested spatial learning in naive
             rats using a mildly stressful water maze task, we found that
             CGP 46381 substantially impaired both the latency to find
             the platform and the path-length travelled in the maze
             during acquisition. CGP 46381-treated rats took longer to
             learn the location of the escape platform and travelled a
             greater distance over the acquisition trials. These data
             demonstrate that GABAB receptor blockade results in a
             suppression of hippocampal long-term potentiation in vivo
             and impairs spatial learning in a task where stress may be a
             component of performance.},
   Doi = {10.1016/0306-4522(96)00131-5},
   Key = {fds274418}
}

@article{fds274503,
   Author = {Levin, ED and Kim, P and Meray, R},
   Title = {Chronic nicotine working and reference memory effects in the
             16-arm radial maze: interactions with D1 agonist and
             antagonist drugs.},
   Journal = {Psychopharmacology},
   Volume = {127},
   Number = {1},
   Pages = {25-30},
   Year = {1996},
   Month = {September},
   ISSN = {0033-3158},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/8880940},
   Keywords = {(R)-2,3,4,5-Tetrahydro-8-chloro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol
             • Animals • Dopamine Agonists • Dopamine
             Antagonists • Drug Interactions • Female •
             Maze Learning • Nicotine • Phenanthridines •
             Rats • Rats, Sprague-Dawley • Receptors, Dopamine
             D1 • antagonists & inhibitors • drug effects*
             • pharmacology • pharmacology*},
   Abstract = {Chronic nicotine infusion has been found in a series of
             studies in our laboratory to significantly improve choice
             accuracy of rats in the eight-arm radial maze. The current
             study was designed to compare the effects of chronic
             nicotine infusion on working and reference memory in a
             16-arm radial maze. Nicotine was administered to female
             Sprague-Dawley rats at approximately 5 mg/kg per day SC via
             osmotic minipumps. Controls received saline infusions.
             Chronic nicotine infusion significantly lowered the number
             of working memory errors compared to controls, whereas the
             number of reference memory errors was not significantly
             affected. The modest nicotine-induced reduction in working
             memory errors was seen as a main effect over the 4 weeks of
             infusion, but the clearest effect was seen in weeks 3-4 of
             nicotine administration. For the 2 weeks after withdrawal,
             the nicotine effect was no longer evident. Acute D1
             challenges were given with the D1 agonist dihydrexidine (0,
             0.25, 0.5 and 1 mg/kg) and the D1 antagonist SCH 23390 (0,
             0.005, 0.015 and 0.05 micrograms/kg) during weeks 3-4 of
             chronic nicotine administration and weeks 1-2 after
             withdrawal from nicotine. Dihydrexidine caused a modest
             dose-related increase in reference memory errors but not
             working memory errors in the nicotine-treated, but not the
             control rats. The D1 antagonist SCH 23390 caused a modest
             though significant decrease in reference memory errors but
             not working memory errors in the control, but not the
             nicotine-treated rats. The behavioral specificity of chronic
             nicotine infusion was demonstrated with selective
             improvement in working memory function. Pharmacological
             interactions were seen with chronic nicotine treatment
             increasing responsivity to D1 agonist and decreasing
             responsivity to a D1 antagonist with regard to reference
             memory. The mechanisms of this interaction are still
             undiscovered.},
   Doi = {10.1007/bf02805971},
   Key = {fds274503}
}

@article{fds274488,
   Author = {Kim, JS and Levin, ED},
   Title = {Nicotinic, muscarinic and dopaminergic actions in the
             ventral hippocampus and the nucleus accumbens: effects on
             spatial working memory in rats.},
   Journal = {Brain Research},
   Volume = {725},
   Number = {2},
   Pages = {231-240},
   Year = {1996},
   Month = {July},
   ISSN = {0006-8993},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/8836529},
   Keywords = {Animals • Female • Hippocampus • Maze
             Learning • Mecamylamine • Memory • Muscarinic
             Agonists • Muscarinic Antagonists • Nicotine
             • Nicotinic Agonists • Nicotinic Antagonists
             • Nucleus Accumbens • Pilocarpine • Rats
             • Rats, Sprague-Dawley • Receptors, Dopamine
             • Receptors, Muscarinic • Receptors, Nicotinic
             • Scopolamine • drug effects • pharmacology
             • physiology • physiology*},
   Abstract = {Acetylcholine (ACh) systems have been widely shown to be
             important for memory. In particular, ACh hippocampal neurons
             are critical for memory formation, though ACh innervation of
             other areas such as the nucleus accumbens may also be
             important. There has also been increasing interest in ACh
             and dopaminergic (DA) interactions with regard to short-term
             spatial memory. In a series of studies, we have found that
             ACh and DA agonists and antagonists given systemically
             interact to influence memory. The critical neural loci of
             these interactions are not currently known. In the present
             study, we used local infusion techniques to examine the role
             of ACh and DA transmitter systems in the nucleus accumbens
             and the ventral hippocampus on radial-arm maze (RAM) working
             memory performance. Into the nucleus accumbens of rats, we
             infused the nicotinic ACh agonist nicotine, the nicotinic
             ACh antagonist mecamylamine, the DA agonist apomorphine, or
             the DA antagonist haloperidol. Into the ventral hippocampus,
             we infused nicotine, mecamylamine, the muscarinic ACh
             agonist pilocarpine, or the muscarinic ACh antagonist,
             scopolamine. The nicotinic ACh and DA interaction was tested
             by a hippocampal infusion of mecamylamine alone or together
             with the DA D2 agonist quinpirole given via subcutaneous
             injection. The results confirmed that both nicotinic and
             muscarinic ACh receptors in the ventral hippocampus play a
             significant role in spatial working memory. Blockade of
             either nicotinic or muscarinic ACh receptors caused
             significant impairments in RAM choice accuracy. However,
             infusion of either nicotinic or muscarinic agonists failed
             to improve choice accuracy. The interaction of DA D2 systems
             in different with hippocampal nicotinic blockade than with
             general nicotinic blockade. Systemic administration of
             quinpirole potentiated the amnestic effect of mecamylamine
             infused into the ventral hippocampus, whereas it was
             previously found to reverse the amnestic effect of
             systemically administered mecamylamine. In contrast to the
             significant effects of mecamylamine in the hippocampus, no
             effects were found after infusion into the nucleus
             accumbens. Nicotine also was not found to have a significant
             effect on memory after intra-accumbens infusion. Neither the
             DA agonist apomorphine nor the DA antagonist haloperidol had
             a significant effect on memory after infusion into the
             nucleus accumbens. This study provides support for the
             involvement of nicotinic and muscarinic receptors in the
             ventral hippocampus in memory function. Ventral hippocampal
             nicotinic systems have significant interactions with D2
             systems, but these differ from their systemic interactions.
             In contrast, nicotinic ACh and DA systems in the nucleus
             accumbens were not found in the current study to be
             important for working memory performance in the
             RAM.},
   Doi = {10.1016/0006-8993(96)00213-2},
   Key = {fds274488}
}

@article{fds274401,
   Author = {Levin, ED and Conners, CK and Sparrow, E and Hinton, SC and Erhardt, D and Meck, WH and Rose, JE and March, J},
   Title = {Nicotine effects on adults with attention-deficit/hyperactivity
             disorder.},
   Journal = {Psychopharmacology},
   Volume = {123},
   Number = {1},
   Pages = {55-63},
   Year = {1996},
   Month = {January},
   ISSN = {0033-3158},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/8741955},
   Keywords = {Adult • Analysis of Variance • Attention Deficit
             Disorder with Hyperactivity • Humans • Middle Aged
             • Nicotine • Psychiatric Status Rating Scales
             • Questionnaires • Reaction Time • Smoking
             • drug effects • drug therapy* •
             physiopathology • therapeutic use*},
   Abstract = {Several lines of evidence suggest that nicotine may be
             useful in treating the symptoms of Attention-Deficit/Hyperactivity
             Disorder (ADHD). The current study was an acute,
             placebo-controlled double-blind experiment to determine
             whether nicotine might be useful as an alternative treatment
             of adults with ADHD symptomatology. Six smokers and 11
             nonsmokers who were outpatient referrals for ADHD were
             diagnosed by DSM-IV criteria. Measures of treatment effect
             included the Clinical Global Impressions (CGI) scale,
             Hopkins' symptom check list (SCL-90-R), the Profile of Mood
             States (POMS), Conners' computerized Continuous Performance
             Test (CPT), the Stroop test, and an interval-timing task.
             The smokers underwent overnight deprivation from smoking and
             were given a 21 mg/day nicotine skin patch for 4.5 h during
             a morning session. The nonsmokers were given a 7 mg/day
             nicotine skin patch for 4.5 h during a morning session.
             Active and placebo patches were given in a counter-balanced
             order approximately 1 week apart. Nicotine caused a
             significant overall nicotine-induced improvement on the CGI.
             This effect was significant when only the nonsmokers were
             considered, which indicated that it was not due merely to
             withdrawal relief. Nicotine caused significantly increased
             vigor as measured by the POMS test. Nicotine caused an
             overall significant reduction in reaction time (RT) on the
             CPT, as well as, with the smokers, a significant reduction
             in another index of inattention, variability in reaction
             time over trial blocks. Nicotine improved accuracy of time
             estimation and lowered variability of time-estimation
             response curves. Because improvements occurred among
             nonsmokers, the nicotine effect appears not to be merely a
             relief of withdrawal symptoms. It is concluded that nicotine
             deserves further clinical trials with ADHD.},
   Doi = {10.1007/BF02246281},
   Key = {fds274401}
}

@article{fds274435,
   Author = {Levin, ED and Torry, D},
   Title = {Acute and chronic nicotine effects on working memory in aged
             rats.},
   Journal = {Psychopharmacology},
   Volume = {123},
   Number = {1},
   Pages = {88-97},
   Year = {1996},
   Month = {January},
   ISSN = {0033-3158},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/8741959},
   Keywords = {Age Factors • Aging • Animals • Dose-Response
             Relationship, Drug • Haloperidol • Male •
             Maze Learning • Mecamylamine • Memory •
             Nicotine • Rats • Rats, Sprague-Dawley •
             Scopolamine • drug effects • drug effects* •
             pharmacology • pharmacology* •
             physiology*},
   Abstract = {Acute and chronic nicotine administration has been
             repeatedly been found in our laboratory to improve working
             memory performance of normal adult rats in the radial-arm
             maze. The current study was conducted to determine if acute
             or chronic nicotine administration would improve working
             memory performance in aged rats. Sixteen young adult (3-7
             months) and 32 aged (24-28 months) male Sprague-Dawley rats
             were trained on an eight-arm radial maze. A significant
             age-related choice deficit was seen during the 21 sessions
             of training. After training, half of the rats in each age
             group were implanted with nicotine-containing osmotic
             minipumps and the other half implanted with
             vehicle-containing pumps. Consistent with previous work, the
             young adult rats given chronic nicotine (approximately 5
             mg/kg per day as measured as nicotine base) showed a
             significant improvement in working memory performance. In
             contrast, the aged rats did not show a significant effect of
             this dose of chronic nicotine. After a 2 week withdrawal
             period the remaining rats underwent a series of acute drug
             challenges with nicotinic and muscarinic agonists and
             antagonists as well as the dopaminergic antagonist
             haloperidol. Mecamylamine and haloperidol impaired the
             memory performance of the young adult rats, whereas the aged
             rats showed no effect. In contrast, scopolamine impaired
             performance of both young adult and aged rats in a similar
             manner. Both pilocarpine and nicotine improved the memory
             performance of the aged rats, but did not improve the young
             adult rats, possibly due to a ceiling effect on performance.
             During the cholinergic agonist drug phase, the aged rats
             which had previously been given chronic nicotine infusions
             showed better performance than those which had not. The
             resistance of the aged rats to chronic nicotine-induced
             working memory improvements and acute mecamylamine-induced
             working memory deficits may have resulted from the decline
             in nicotinic receptors seen with aging. Chronic
             co-administration of the nicotinic antagonist mecamylamine
             in a previous study was found to abolish the chronic
             nicotine-induced working memory improvement. The aged rats
             were resistant to haloperidol-induced deficits which may
             have resulted from the decrease in dopaminergic receptors
             seen with aging. Interestingly, acute cholinergic agonists
             including nicotine did improve working memory performance in
             the aged rats and previous chronic nicotine infusion was
             beneficial during the period of acute cholinergic agonist
             challenge. This suggests that nicotinic treatment may be of
             use for treating age associated memory impairments but that
             special dosing regimens may be required.},
   Doi = {10.1007/bf02246285},
   Key = {fds274435}
}

@article{fds274409,
   Author = {Conners, CK and Levin, ED and Sparrow, E and Hinton, SC and Erhardt, D and Meck, WH and Rose, JE and March, J},
   Title = {Nicotine and attention in adult attention deficit
             hyperactivity disorder (ADHD).},
   Journal = {Psychopharmacology Bulletin},
   Volume = {32},
   Number = {1},
   Pages = {67-73},
   Year = {1996},
   ISSN = {0048-5764},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/8927677},
   Keywords = {Adult • Attention Deficit Disorder with Hyperactivity
             • Double-Blind Method • Female • Humans
             • Male • Nicotine • Prognosis •
             Psychiatric Status Rating Scales • administration &
             dosage* • adverse effects • drug
             therapy*},
   Abstract = {Nicotine, like the psychostimulants methylphenidate and
             dextroamphetamine, acts as an indirect dopamine agonist and
             improves attention and arousal. Adults and adolescents with
             attention deficit hyperactivity disorder (ADHD) smoke much
             more frequently than normal individuals or those with other
             psychiatric conditions, perhaps as a form of self-medication
             for ADHD symptoms. Nicotine might therefore have some value
             as a treatment for ADHD. The present study is an acute
             double-blind crossover administration of nicotine and
             placebo with smokers (n = 6) and nonsmokers (n = 11)
             diagnosed with adult ADHD. The drug was delivered via a
             transdermal patch at a dosage of 7 mg/day for nonsmokers and
             21 mg/day for smokers. Results indicate significant
             clinician-rated global improvement, self-rated vigor and
             concentration, and improved performance on chronometric
             measures of attention and timing accuracy. Side effects were
             minimal. These acute results indicate the need for a longer
             clinical trial and a comparison with other stimulants in
             adult ADHD treatment.},
   Key = {fds274409}
}

@article{fds274464,
   Author = {Levin, ED},
   Title = {Pergolide interactions with nicotine and pilocarpine in rats
             on the radial-arm maze.},
   Journal = {Pharmacology, Biochemistry, and Behavior},
   Volume = {52},
   Number = {4},
   Pages = {837-840},
   Year = {1995},
   Month = {December},
   ISSN = {0091-3057},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/8587928},
   Keywords = {Animals • Dose-Response Relationship, Drug • Drug
             Interactions • Female • Maze Learning •
             Nicotine • Pergolide • Pilocarpine • Rats
             • Rats, Sprague-Dawley • drug effects* •
             pharmacology*},
   Abstract = {Antagonists of nicotinic and muscarinic acetylcholinergic
             (ACh) receptors have significant interactions with
             dopaminergic (DA) ligands with regard to radial-arm maze
             choice accuracy. The current studies examined the
             interactions of agonists of nicotinic and muscarinic ACh
             receptors with the DA agonist pergolide. Pergolide given in
             a range from 0.03-1.0 mg/kg had no detectable effect on
             radial-arm maze choice accuracy when given alone. With this
             dose range there was a linear increase in response latency.
             Pergolide had significant interactive effects with the
             nicotinic and muscarinic agonists nicotine and pilocarpine.
             Given together with nicotine, pergolide produced a
             significantly elevated linear increase in accuracy relative
             to when it was given alone. With pilocarpine, pergolide had
             an inverted U-shaped effect improving choice accuracy at low
             to moderate doses of 0.03 and 0.1 mg/kg. These results
             support previous findings of DA-ACh interactions with regard
             to radial-arm maze choice accuracy. Combined DA-ACh
             treatment may be a useful treatment of cognitive
             dysfunction.},
   Doi = {10.1016/0091-3057(95)00165-s},
   Key = {fds274464}
}

@article{fds274357,
   Author = {Beckham, JC and Roodman, AA and Shipley, RH and Hertzberg, MA and Cunha,
             GH and Kudler, HS and Levin, ED and Rose, JE and Fairbank,
             JA},
   Title = {Smoking in Vietnam combat veterans with post-traumatic
             stress disorder.},
   Journal = {Journal of Traumatic Stress},
   Volume = {8},
   Number = {3},
   Pages = {461-472},
   Year = {1995},
   Month = {July},
   ISSN = {0894-9867},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/7582610},
   Keywords = {Adult • Combat Disorders • Comorbidity •
             Cross-Sectional Studies • Humans • Incidence
             • Male • Middle Aged • Motivation •
             North Carolina • Personality Inventory • Smoking
             • Smoking Cessation • Veterans • Vietnam
             • epidemiology • psychology • psychology*
             • statistics & numerical data},
   Abstract = {The present study investigated smoking prevalence, smoking
             motives, demographic variables and psychological symptoms in
             124 help-seeking, male Vietnam combat veterans with
             post-traumatic stress disorder (PTSD). A high percentage of
             these veterans smoked (60%). Vietnam veterans with PTSD who
             smoked were more likely than those who did not smoke to
             report higher levels of PTSD symptoms, depression and trait
             anxiety. Increased depression was associated with increased
             automatic smoking. Smokers reported a high frequency of
             smoking in response to military memories. Implications for
             smoking interventions, cessation, and relapse prevention
             efforts are discussed.},
   Doi = {10.1007/bf02102970},
   Key = {fds274357}
}

@article{fds274456,
   Author = {Levin, ED and Rose, JE and Abood, L},
   Title = {Effects of nicotinic dimethylaminoethyl esters on working
             memory performance of rats in the radial-arm
             maze.},
   Journal = {Pharmacology, Biochemistry, and Behavior},
   Volume = {51},
   Number = {2-3},
   Pages = {369-373},
   Year = {1995},
   Month = {June},
   ISSN = {0091-3057},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/7667355},
   Keywords = {Animals • Dose-Response Relationship, Drug •
             Female • Maze Learning • Memory, Short-Term •
             Nicotine • Nicotinic Acids • Nicotinic Agonists
             • Rats • Rats, Sprague-Dawley • Receptors,
             Nicotinic • drug effects • drug effects* •
             pharmacology • pharmacology*},
   Abstract = {Nicotine has been found to improve memory performance in a
             variety of tests, including the radial-arm maze. This
             improvement, together with the consistent finding of a
             decline in cortical nicotinic receptor concentration in
             Alzheimer's patients, has fueled the search for novel
             nicotinic ligands with therapeutic potential. In the current
             studies, a series of nicotinic compounds was tested for
             effects on working memory performance in the radial-arm
             maze. One of the three compounds tested, DMAE II
             (dimethylaminoethanol cyclohexyl carboxylate fumurate),
             produced significant improvements in working memory
             performance. In the first experiment, this drug produced a
             biphasic dose-response curve with improved performance at
             the 20-mg/kg dose but not at 10 or 40 mg/kg. In a second
             round of DMAE II administration, the same rats showed a
             significant improvement with the 40-mg/kg dose. In the
             second experiment, a new set of rats also showed a biphasic
             dose-response to DMAE II. The 20-mg/kg dose caused a
             significant improvement whereas the 40-mg/kg dose did not.
             Interactions of DMAE II with nicotine and mecamylamine were
             also studied. Nicotine (0.2 mg/kg) by itself caused a
             significant improvement in working memory performance. No
             additive effects of DMAE II with nicotine were seen. In
             fact, some attenuation of response was seen with the
             combination. Choice accuracy data for mecamylamine could not
             be analyzed because of excessive sedation and nonresponding.
             These studies show that, like nicotine, the nicotinic ligand
             DMAE II causes an improvement in radial-arm mace choice
             accuracy. The lack of additivity with nicotine may have been
             to the partial agonist effects of DMAE II.},
   Doi = {10.1016/0091-3057(94)00406-9},
   Key = {fds274456}
}

@article{fds274348,
   Author = {Rose, JE and Levin, ED and Behm, FM and Westman, EC and Stein, RM and Lane,
             JD and Ripka, GV},
   Title = {Combined administration of agonist-antagonist as a method of
             regulating receptor activation.},
   Journal = {Annals of the New York Academy of Sciences},
   Volume = {757},
   Pages = {218-221},
   Year = {1995},
   Month = {May},
   ISSN = {0077-8923},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/7611676},
   Keywords = {Blood Pressure • Humans • Mecamylamine •
             Nicotine • Receptors, Cholinergic • Smoking •
             drug effects • drug effects* •
             pharmacology*},
   Doi = {10.1111/j.1749-6632.1995.tb17478.x},
   Key = {fds274348}
}

@article{fds274490,
   Author = {Levin, ED and Rose, JE},
   Title = {Acute and chronic nicotinic interactions with dopamine
             systems and working memory performance.},
   Journal = {Annals of the New York Academy of Sciences},
   Volume = {757},
   Pages = {245-252},
   Year = {1995},
   Month = {May},
   ISSN = {0077-8923},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/7611680},
   Keywords = {Animals • Dopamine • Drug Administration Schedule
             • Humans • Maze Learning • Mecamylamine
             • Memory • Nicotine • Receptors, Nicotinic
             • Substantia Nigra • Ventral Tegmental Area •
             administration & dosage* • drug effects •
             pharmacology* • physiology • physiology*},
   Abstract = {Nicotine has been found to improve memory performance in a
             variety of tests in rats, monkeys, and humans. Interactions
             of nicotinic systems with dopamine (DA) systems may be
             important for this effect. We conducted a series of studies
             of nicotinic agonist and antagonist interactions with DA
             systems using rats in a win-shift working memory task in the
             radial-arm maze. The working memory deficit caused by the
             nicotinic antagonist mecamylamine was potentiated by the
             D1/D2 DA antagonist haloperidol and the specific D2
             antagonist raclopride. In contrast, the mecamylamine-induced
             deficit was reversed by co-administration of the D2/D3
             agonist quinpirole. Nicotine also has significant
             interactions with dopamine drugs with regard to working
             memory performance in the radial-arm maze. The DA agonist
             pergolide did not by itself improve radial-arm maze memory
             performance, but when given together with nicotine it
             produced an elevated dose-dependent increase in choice
             accuracy. The D1 agonist SKF 38393 significantly impaired
             radial-arm maze choice accuracy. Nicotine was effective in
             reversing this deficit. When given together with nicotine,
             the D2/D3 agonist quinpirole improved RAM choice accuracy
             relative to either drug alone. Acute local infusion of
             mecamylamine to the midbrain DA nuclei effectively impairs
             working memory function in the radial-arm maze. In contrast
             to acute nicotinic manipulations, considerably less evidence
             exists that the effects of chronic nicotine administration
             are influenced by DA systems. This may be an example of the
             different neural substrates that underlie the memory
             improvement caused by acute and chronic nicotine.},
   Doi = {10.1111/j.1749-6632.1995.tb17481.x},
   Key = {fds274490}
}

@article{fds274450,
   Author = {McEvoy, JP and Freudenreich, O and Levin, ED and Rose,
             JE},
   Title = {Haloperidol increases smoking in patients with
             schizophrenia.},
   Journal = {Psychopharmacology},
   Volume = {119},
   Number = {1},
   Pages = {124-126},
   Year = {1995},
   Month = {May},
   ISSN = {0033-3158},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/7675943},
   Keywords = {Adult • Carbon Monoxide • Female •
             Haloperidol • Humans • Male • Middle Aged
             • Nicotine • Schizophrenia • Smoking* •
             blood • pharmacology*},
   Abstract = {Ten patients with schizophrenia participated in 120-min
             free-smoking sessions when actively psychotic and free of
             antipsychotic medications, and again after the initiation of
             haloperidol treatment. During these free-smoking sessions
             they had access to cigarettes ad libitum. Their expired air
             carbon monoxide (CO) and plasma nicotine and cotinine levels
             were measured at the end of the 120-min free-smoking
             sessions. These patients smoked more after starting
             haloperidol treatment, relative to their baseline rate of
             smoking when free of antipsychotic medications, as evidenced
             by significantly higher expired CO and plasma nicotine
             levels.},
   Doi = {10.1007/bf02246063},
   Key = {fds274450}
}

@article{fds274210,
   Author = {McEvoy, J and Freudenreich, O and McGee, M and VanderZwaag, C and Levin,
             E and Rose, J},
   Title = {Clozapine decreases smoking in patients with chronic
             schizophrenia.},
   Journal = {Biological Psychiatry},
   Volume = {37},
   Number = {8},
   Pages = {550-552},
   Year = {1995},
   Month = {April},
   ISSN = {0006-3223},
   url = {http://dx.doi.org/10.1016/0006-3223(94)00365-A},
   Doi = {10.1016/0006-3223(94)00365-A},
   Key = {fds274210}
}

@article{fds274334,
   Author = {Sudan, BJ},
   Title = {Nicotine skin patch treatment and adverse reactions: skin
             irritation, skin sensitization, and nicotine as a
             hapten.},
   Journal = {Journal of Clinical Psychopharmacology},
   Volume = {15},
   Number = {2},
   Pages = {145-146},
   Year = {1995},
   Month = {April},
   url = {http://dx.doi.org/10.1097/00004714-199504000-00016},
   Doi = {10.1097/00004714-199504000-00016},
   Key = {fds274334}
}

@article{fds274373,
   Author = {Levin, ED and Christopher, NC and Abou-Donia, MB},
   Title = {Triphenyl phosphite-induced impairment of spatial
             alternation learning.},
   Journal = {Journal of Toxicology and Environmental Health},
   Volume = {44},
   Number = {4},
   Pages = {461-467},
   Year = {1995},
   Month = {April},
   ISSN = {0098-4108},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/7723078},
   Keywords = {Aging • Animals • Injections, Intraperitoneal
             • Male • Maze Learning • Phosphites •
             Rats • Rats, Sprague-Dawley • Time Factors •
             administration & dosage • drug effects* •
             psychology • toxicity*},
   Abstract = {Triphenyl phosphite (TPP) is a weak acetylcholinesterase
             inhibitor and a type II organophosphorus compound-induced
             delayed neurotoxic agent. The current study examined the
             cognitive effects of a single 250 mg/kg ip dose of TPP
             administered to either 3-mo- or 1-yr-old male Sprague-Dawley
             rats. Starting 4 d after TPP administration, the rats began
             training on a T-maze spatial alternation task for food
             reinforcement. Over five sessions of acquisition training,
             the TPP-treated rats showed significantly lower alternation
             scores than controls. There was no difference in spatial
             alternation performance in the first session, when both
             groups were performing at near-chance levels. In sessions
             2-5, the controls improved dramatically to an average of
             85.3 +/- 3.2% correct, while the TPP-treated rats did not
             significantly change, with 69.7 +/- 3.1 percent correct.
             During sessions 2 and 3 there was a significant TPP
             treatment-related deficit. This TPP-induced choice accuracy
             deficit was persistent in that it was seen well after the
             acute exposure. With continued training the TPP-exposed rats
             were able to learn the task as well as controls. There were
             no significant TPP effects on response latency. These data
             show that acute TPP administration has persistent effects of
             impairing T-maze learning that do not appear to result from
             effects on motor function.},
   Doi = {10.1080/15287399509531974},
   Key = {fds274373}
}

@article{fds316080,
   Author = {CUTLER, AR and WILKERSON, AE and GINGRAS, JL and LEVIN,
             ED},
   Title = {PRENATAL COCAINE AND NICOTINE EXPOSURE IN RATS - EFFECTS ON
             LONG-TERM COGNITIVE OUTCOME AND SEXUAL-DIFFERENTIATION},
   Journal = {Pediatric Research},
   Volume = {37},
   Number = {4},
   Pages = {A14-A14},
   Publisher = {WILLIAMS & WILKINS},
   Year = {1995},
   Month = {April},
   ISSN = {0031-3998},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:A1995QP08200070&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Key = {fds316080}
}

@article{fds316083,
   Author = {Levin, ED},
   Title = {Reply},
   Journal = {Journal of Clinical Psychopharmacology},
   Volume = {15},
   Number = {2},
   Pages = {146-146},
   Publisher = {Ovid Technologies (Wolters Kluwer Health)},
   Year = {1995},
   Month = {April},
   ISSN = {0271-0749},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:A1995QN55900016&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Doi = {10.1097/00004714-199504000-00017},
   Key = {fds316083}
}

@article{fds274378,
   Author = {Bushnell, PJ and Levin, ED and Overstreet, DH},
   Title = {Spatial working and reference memory in rats bred for
             autonomic sensitivity to cholinergic stimulation:
             acquisition, accuracy, speed, and effects of cholinergic
             drugs.},
   Journal = {Neurobiology of Learning and Memory},
   Volume = {63},
   Number = {2},
   Pages = {116-132},
   Year = {1995},
   Month = {March},
   ISSN = {1074-7427},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/7663885},
   Keywords = {Animals • Arousal • Autonomic Nervous System
             • Body Temperature Regulation • Body Weight •
             Cholinergic Agents • Conditioning, Operant •
             Discrimination Learning • Drinking • Genotype*
             • Isoflurophate • Male • Maze Learning •
             Mental Recall • Motivation • Orientation •
             Oxotremorine • Pattern Recognition, Visual • Rats
             • Rats, Inbred Strains • Reaction Time •
             Receptors, Muscarinic • Receptors, Nicotinic •
             Selection (Genetics) • Species Specificity • drug
             effects • drug effects* • genetics •
             pharmacology • pharmacology*},
   Abstract = {Rat lines were selected by breeding for sensitivity to signs
             of autonomic stimulation (hypotherma, loss of body weight,
             and reduced water intake) induced by the cholinesterase
             inhibitor diisopropyl fluorophosphate (DFP). These lines
             have since been maintained for 10 generations by continued
             selection for hypothermic responsiveness to the muscarinic
             agonist oxotremorine. The sensitive rats (Flinders Sensitive
             Line, FSL) differ from the resistant rats (Flinders
             Resistant Line, FRL) both neurochemically and behaviorally,
             particularly in aversively motivated test situations in
             which response speed is assessed. This study was conducted
             to determine whether the selected differences in cholinergic
             autonomic sensitivity would be expressed as differences in
             cognitive ability based on choice accuracy in appetitive
             tasks. The working and reference memory of rats of these two
             strains was thus assessed using operant delayed
             matching-to-position/visual discrimination (DMTP/VD) and the
             radial-arm maze. A Long-Evans (L-E) reference group was
             included in the DMTP/VD study. FSL rats responded more
             slowly than the other rats during acquisition of both tasks,
             but showed no differences in response accuracy either during
             acquisition or during asymptotic performance of either task.
             In addition, challenges with muscarinic and nicotinic
             antagonists and agonists [scopolamine (0.06-1.0 mg/kg),
             pilocarpine (1.0-4.0 mg/kg), mecamylamine (1.0-10.0 mg/kg),
             and nicotine (0.1-0.3 mg/kg)] demonstrated predicted
             differences in sensitivity among the lines only on
             performance measures such as response latency and trial
             completion. Counter to prediction, the sensitivity of the
             FRL rats to the ability of scopolamine to reduce matching
             accuracy was lower than those of the L-E and FSL rats. Thus
             selection based upon physiological endpoints related to
             cholinergic autonomic homeostasis did not produce analogous
             differences in cognitive function in rats.},
   Doi = {10.1006/nlme.1995.1012},
   Key = {fds274378}
}

@article{fds274498,
   Author = {Westman, EC and Levin, ED and Rose, JE},
   Title = {Nicotine as a therapeutic drug.},
   Journal = {North Carolina Medical Journal},
   Volume = {56},
   Number = {1},
   Pages = {48-51},
   Year = {1995},
   Month = {January},
   ISSN = {0029-2559},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/7862206},
   Keywords = {Alzheimer Disease • Colitis, Ulcerative • Humans
             • Nicotine • Parkinson Disease • drug
             therapy* • pharmacology • therapeutic
             use*},
   Abstract = {Current evidence about the therapeutic potential of nicotine
             is strongest for ulcerative colitis. The role, if any, of
             nicotine therapy in Parkinson's or Alzheimer's diseases is
             not clear, but further research appears warranted. We need
             more information about the tolerability and safety of
             nicotine administration in such diseases. At present, any
             therapeutic trials of nicotine therapy should occur only as
             part of research protocols. Further nonjudgmental
             examination of the perceived effects of tobacco use may lead
             to other uses of nicotine. However, given the widespread
             morbidity and mortality directly attributable to tobacco
             use, no form of tobacco should be used to deliver nicotine.
             We encourage everyone who uses tobacco products to
             quit.},
   Key = {fds274498}
}

@article{fds136393,
   Title = {Levin ED and D Torry. Nicotine effects on memory
             performance. In: International Symposium on Nicotine: The
             Effects of Nicotine on Biological Systems II, P.B.S. Clarke,
             M. Quik, K. Thurau and F. Adlkofer (Eds.), BirkhŠuser,
             Boston, pp 329-335, 1995.},
   Year = {1995},
   Key = {fds136393}
}

@article{fds136394,
   Title = {Levin ED and JE Rose. Acute and chronic nicotinic
             interactions with dopamine systems and working memory
             performance. In: Annals of the New York Academy of Sciences,
             Vol 757, Functional Diversity of Interacting Receptors, A.
             Lajtha and L. Abood (eds.), The New York Academy of
             Sciences, New York, pp 245-252, 1995.},
   Year = {1995},
   Key = {fds136394}
}

@article{fds136395,
   Title = {Levin ED, NC Christopher MB Abou-Donia. Triphenyl
             phosphite-induced impairment of spatial alternation. Journal
             of Toxicology and Environmental Health, 44:461-467,
             1995.},
   Year = {1995},
   Key = {fds136395}
}

@article{fds274508,
   Author = {Andrén, PE and Levin, ED and Liminga, U and Gunne,
             L},
   Title = {Behavioral and neurochemical consequences of ibotenic acid
             lesion in the subthalamic nucleus of the common
             marmoset.},
   Journal = {Brain Research Bulletin},
   Volume = {36},
   Number = {3},
   Pages = {301-307},
   Year = {1995},
   ISSN = {0361-9230},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/7697384},
   Keywords = {Acetylcholine • Animals • Basal Ganglia •
             Behavior, Animal • Brain Chemistry • Callithrix
             • Dopamine • Female • Ibotenic Acid •
             Inferior Colliculus • Male • drug effects* •
             gamma-Aminobutyric Acid • physiology},
   Abstract = {Five marmosets were unilaterally lesioned within the
             subthalamic nucleus (STN) by injection of 10 micrograms
             ibotenic acid. Seven marmosets served as saline injected
             controls. The lesioned marmosets showed an increased
             locomotor activity, occasional tongue protrusions, posture
             asymmetry, and abnormal movements of the contralateral legs
             and arms. The animals were sacrificed 21 days after the
             ibotenic acid injection and markers of gamma-aminobutyric
             acid (GABA), dopamine (DA), and acetylcholine were studied
             in a variety brain regions. There was a bilateral increase
             in the activity of glutamic acid decarboxylase (GAD) in the
             caudate, putamen, globus pallidus, superior colliculus, and
             the ventral anterior/ventral lateral (VA/VL) thalamus,
             whereas GABA concentrations were only increased
             ipsilaterally in the ventral posterior medial/centromedial/parafasciculus
             (VPM/CM/Pf) complex of the thalamus. Tyrosine hydroxylase
             (TH) activity was bilaterally increased in the medial
             segment of globus pallidus and nucleus accumbens. However,
             there were also changes restricted to the side contralateral
             to the lesion. TH activity and DA concentrations were
             increased contralateral to the lesion in the putamen.
             Choline acetyltransferase (CAT) activity was bilaterally
             increased in the medial segment of globus pallidus and
             hypothalamus. The ibotenic acid induced STN-lesion in the
             marmoset, thus, seemed to cause a widespread bilateral
             activation of neurons within the basal ganglia.},
   Doi = {10.1016/0361-9230(94)00206-g},
   Key = {fds274508}
}

@article{fds274437,
   Author = {Kotlova, EK and Levin, ED and Iusupova, MP and Rozynov, BV and Stepanov,
             VM},
   Title = {[A transformylation reaction--transfer of an N-formyl
             residue to amino acids and peptides in nucleophilic
             groups--as a side reaction of peptide synthesis].},
   Journal = {Bioorganicheskaia Khimiia},
   Volume = {20},
   Number = {11},
   Pages = {1186-1195},
   Year = {1994},
   Month = {November},
   ISSN = {0132-3423},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/7880178},
   Keywords = {Acyltransferases • Amino Acids • Carboxylic Acids
             • Chromatography, High Pressure Liquid • Esters
             • Hydroxymethyl and Formyl Transferases* • Mass
             Spectrometry • Peptides • chemistry*},
   Abstract = {The formyl group transfer from N-formyl amino acids and
             their derivatives to other acceptors--amino acids esters and
             aniline, was studied. Formylamino acids with the free
             alpha-carboxyl group are more effective donors in
             transformylation than formyl peptides or esters of
             formylamino acids.},
   Key = {fds274437}
}

@article{fds274506,
   Author = {Levin, ED and Briggs, SJ and Christopher, NC and Auman,
             JT},
   Title = {Working memory performance and cholinergic effects in the
             ventral tegmental area and substantia nigra.},
   Journal = {Brain Research},
   Volume = {657},
   Number = {1-2},
   Pages = {165-170},
   Year = {1994},
   Month = {September},
   ISSN = {0006-8993},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/7820615},
   Keywords = {Acetylcholine • Alkaloids • Animals •
             Azocines • Female • Maze Learning •
             Mecamylamine • Memory • Nicotine •
             Pilocarpine • Psychomotor Performance •
             Quinolizines • Rats • Rats, Sprague-Dawley •
             Scopolamine • Substantia Nigra • Ventral Tegmental
             Area • pharmacology • physiology*},
   Abstract = {The nicotinic antagonist mecamylamine has been found to
             impair working memory performance in the radial-arm maze
             (RAM) after s.c. or i.c.v. administration. Mecamylamine has
             important interactions with dopaminergic (DA) systems.
             Mecamylamine-induced memory deficits in the RAM are
             potentiated by the D2 antagonist raclopride and reversed by
             the D2 agonist quinpirole. The nicotinic agonist nicotine
             has been found to improve working memory performance in the
             RAM after s.c. or i.c.v. administration. Nicotine-induced
             memory improvement in the RAM is potentiated by the D2
             agonist quinpirole. The midbrain DA nuclei, the substantia
             nigra (SN) and the ventral tegmental area (VTA) have
             relatively dense concentrations of nicotinic receptors which
             may be critical sites of action for mecamylamine and
             nicotine. In the current study, the effects of mecamylamine
             (1, 3.3 and 10 micrograms/side) infusions into the SN (n =
             12) and VTA (n = 13) on working memory in the radial-arm
             maze were examined in adult female Sprague-Dawley rats. The
             10-micrograms/side dose of mecamylamine significantly
             impaired radial-arm maze working memory performance when
             infused into either the SN or VTA. No significant effects of
             mecamylamine on response latency were seen. The nicotinic
             agonists cytisine (0.1, 0.33 and 1.0 microgram/side) and
             nicotine (0.3, 1.0 and 3.3 micrograms/side) were
             administered in a counterbalanced order. The high dose of
             cytisine (1 microgram/side) nearly caused a significant
             deficit in choice accuracy. Nicotine slightly depressed
             choice accuracy but not significantly in this study. The
             interaction of nicotine and mecamylamine was then studied. A
             dose of 1.0 microgram/side of nicotine caused a significant
             decrease in choice accuracy. Interestingly, this was
             significantly reversed by a 3.3-micrograms/side dose of
             mecamylamine.(ABSTRACT TRUNCATED AT 250 WORDS)},
   Doi = {10.1016/0006-8993(94)90964-4},
   Key = {fds274506}
}

@article{fds274419,
   Author = {Rose, JE and Behm, FM and Westman, EC and Levin, ED and Stein, RM and Ripka, GV},
   Title = {Mecamylamine combined with nicotine skin patch facilitates
             smoking cessation beyond nicotine patch treatment
             alone.},
   Journal = {Clinical Pharmacology and Therapeutics},
   Volume = {56},
   Number = {1},
   Pages = {86-99},
   Year = {1994},
   Month = {July},
   ISSN = {0009-9236},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/8033499},
   Keywords = {Administration, Cutaneous • Adult • Affect •
             Blood Pressure • Breath Tests • Carbon Monoxide
             • Double-Blind Method • Drug Therapy, Combination
             • Female • Heart Rate • Humans • Male
             • Mecamylamine • Nicotine • Patient
             Compliance • Smoking Cessation • Substance
             Withdrawal Syndrome • Treatment Outcome •
             administration & dosage • adverse effects •
             analysis • drug effects • etiology • methods*
             • therapeutic use*},
   Abstract = {OBJECTIVE: To evaluate concurrent administration of
             mecamylamine (nicotine antagonist) with nicotine skin patch
             treatment for smoking cessation. METHODS: This was a
             randomized, double-blind, placebo-controlled trial.
             Forty-eight healthy smokers who smoked at least one pack per
             day were studied at an outpatient smoking cessation research
             clinic. The subjects ranged in age from 20 to 40 years.
             Intervention with the nicotine skin patch (6 to 8 weeks)
             plus oral mecamylamine (2.5 to 5 mg twice a day for 5 weeks)
             was compared to nicotine patch plus placebo. Mecamylamine
             treatment began 2 weeks before smoking cessation. The
             primary outcome was continuous abstinence through 7 weeks
             after cessation (1 week after treatment), confirmed by
             expired air carbon monoxide measurements. Secondary measures
             included point abstinence at 7 weeks, continuous abstinence
             at 6- and 12-month follow-up, and self-reported withdrawal
             symptoms. RESULTS: The continuous abstinence rate at 7 weeks
             was three times higher in the mecamylamine condition: 50%
             versus 16.7%, p = 0.015. Point abstinence at 7 weeks was 58%
             for mecamylamine versus 29% for placebo, p = 0.044. At
             follow-up, continuous abstinence remained higher for
             mecamylamine: 37.5% versus 12.5% at 6 months (p = 0.046) and
             37.5% versus 4.2% at 12 months (p = 0.004). Mecamylamine
             also significantly reduced craving for cigarettes, negative
             affect, and appetite. CONCLUSIONS: Agonist-antagonist
             therapy, consisting of the nicotine patch with oral
             mecamylamine, may substantially improve current smoking
             cessation treatment.},
   Doi = {10.1038/clpt.1994.105},
   Key = {fds274419}
}

@article{fds274426,
   Author = {Levin, ED and Westman, EC and Stein, RM and Carnahan, E and Sanchez, M and Herman, S and Behm, FM and Rose, JE},
   Title = {Nicotine skin patch treatment increases abstinence,
             decreases withdrawal symptoms, and attenuates rewarding
             effects of smoking.},
   Journal = {Journal of Clinical Psychopharmacology},
   Volume = {14},
   Number = {1},
   Pages = {41-49},
   Year = {1994},
   Month = {February},
   ISSN = {0271-0749},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/8151002},
   Keywords = {Administration, Cutaneous • Adult • Arousal •
             Breath Tests • Carbon Monoxide • Double-Blind
             Method • Female • Humans • Male • Middle
             Aged • Motivation* • Nicotine • Smoking
             • Smoking Cessation • Substance Withdrawal
             Syndrome • administration & dosage* • adverse
             effects • drug effects • drug therapy •
             methods* • pharmacokinetics • psychology •
             psychology*},
   Abstract = {A variety of studies have shown that nicotine skin patches
             are effective in promoting smoking cessation. This study
             replicated this effect, in addition, nicotine skin patches
             were found to decrease a variety of withdrawal effects,
             including craving for cigarettes, negative affect,
             hypoarousal, and increased appetite. This study also
             assessed the depressive symptoms shown by smokers before and
             after they quit smoking. Control subjects showed a
             significant increase in depressive symptoms after smoking
             cessation, whereas the subjects given the nicotine skin
             patch were not as affected. If the subjects slipped and
             smoked a cigarette during the time they were wearing the
             patch, they were asked to rate the effects of that
             cigarette. These "slip" cigarettes were rated significantly
             lower in satisfaction and good taste by subjects in the
             nicotine patch group than by controls. The nicotine skin
             patch may improve smoking cessation rates both by reducing
             nicotine withdrawal effects and by reducing the reward of
             slips back to smoking. This latter effect may prove to be
             effective in preventing slips from turning into
             relapses.},
   Key = {fds274426}
}

@article{fds274209,
   Author = {Brucato, FH and Levin, ED and Rose, JE and Swartzwelder,
             HS},
   Title = {Intracerebroventricular nicotine and mecamylamine alter
             radial‐arm maze performance in rats},
   Journal = {Drug Development Research},
   Volume = {31},
   Number = {1},
   Pages = {18-23},
   Publisher = {WILEY},
   Year = {1994},
   Month = {January},
   url = {http://dx.doi.org/10.1002/ddr.430310104},
   Abstract = {In rats, the effects of an intracerebroventricular (ICV)
             nicotinic agonist nicotine (NIC), the nicotinic antagonist
             mecamylamine (MEC), and combinations of NIC + MEC were
             assessed in a radial‐arm maze (RAM). In experiment 1,
             exploratory behavior was assessed in untrained rats (N =
             13). The rats received 4 μg, 8.65 nmol NIC (NIC 4), 200
             μg, 0.98 μmol MEC (MEC), and saline (SAL) ICV infusions.
             NIC 4 caused a significant increase in choice distribution
             compared to SAL (P < 0.025). In experiment 2, rats (N = 10)
             were trained to perform a working memory task for food
             reinforcement in the RAM. ICV doses of SAL, NIC 4, NIC 8,
             MEC, MECNIC 4, and MECNIC 8 were administered after
             completion of the training period. MEC caused a significant
             deficit in choice accuracy when compared to SAL (P < 0.025).
             This deficit was reversed when NIC 8 was coadministered with
             MEC (P < 0.05). There were no significant effects on choice
             latency for either study. The effects of ICV NIC and MEC on
             RAM performance are generally similar to their systemic
             effects in that NIC improves and MEC impairs choice
             accuracy. The reversal of the MEC‐induced choice deficit
             by ICV NIC administration has not been reported with
             systemic administration. ICV MEC induces a choice accuracy
             deficit without increasing choice latency. This has not been
             seen with systemic MEC administration. The current result
             implies that the MEC‐induced choice accuracy deficit did
             not result from MEC‐induced sedation. The data indicate
             that previously reported changes in choice accuracy from
             peripherally administered NIC and MEC result from their
             central effects. © 1994 Wiley‐Liss, Inc. Copyright ©
             1994 Wiley‐Liss, Inc.},
   Doi = {10.1002/ddr.430310104},
   Key = {fds274209}
}

@article{fds274321,
   Author = {Rose, JE and Behm, FM and Westman, EC and Levin, ED and Stein, RM and Lane,
             JD and Ripka, GV},
   Title = {Combined Effects of Nicotine and Mecamylamine in Attenuating
             Smoking Satisfaction},
   Journal = {Experimental and Clinical Psychopharmacology},
   Volume = {2},
   Number = {4},
   Pages = {328-344},
   Publisher = {American Psychological Association (APA)},
   Year = {1994},
   Month = {January},
   ISSN = {1064-1297},
   url = {http://dx.doi.org/10.1037/1064-1297.2.4.328},
   Abstract = {Separate and combined effects of nicotine and the nicotinic
             antagonist mecamylamine were studied. Twelve smokers rated
             test cigarettes after administration of mecamylamine versus
             placebo capsules and nicotine versus nonnicotine preload.
             Smoking withdrawal symptoms, task performance, and
             cardiovascular activity were also measured. Mecamylamine
             attenuated smoking satisfaction, liking, and airway
             sensations. The nicotine preload similarly reduced the
             enjoyable aspects of subsequent test cigarettes, and this
             action of the preload was not prevented by mecamylamine. In
             contrast, mecamylamine blocked nicotine-related increases in
             heart rate and systolic blood pressure. Conversely, nicotine
             counteracted mecamylamine's effects on tapping speed and
             orthostatic blood pressure response. Although each drug
             offset potential side effects of the other, they acted in
             unison to attenuate smoking satisfaction and should be
             evaluated in combination for smoking cessation.},
   Doi = {10.1037/1064-1297.2.4.328},
   Key = {fds274321}
}

@article{fds274332,
   Author = {Levin, ED and Eisner, B},
   Title = {Nicotine interactions with dopamine agonists: Effects on
             working memory function},
   Journal = {Drug Development Research},
   Volume = {31},
   Number = {1},
   Pages = {32-37},
   Publisher = {WILEY},
   Year = {1994},
   Month = {January},
   url = {http://dx.doi.org/10.1002/ddr.430310106},
   Abstract = {Nicotine has been found to improve memory performance in a
             variety of tests including the radial‐arm maze. Nicotine
             may have effects mediated by promoting the release of
             dopamine. The present study was conducted to determine the
             interactions of nicotine with D1 and D2 agonists. Rats were
             acutely administered nicotine, the D1 agonist SKF 38393, and
             D2/D3 agonist quinpirole, and nicotine together with each of
             these agonists. Nicotine significantly improved choice
             accuracy in the radial‐arm maze. The D1 agonist SKF 38393
             significantly impaired choice accuracy. Nicotine was
             effective in reversing this effect. The D2/D3 agonist
             quinpirole showed a trend toward potentiating the
             improvement in choice accuracy caused by 0.2 mg/kg (0.43
             μmol/kg) of nicotine. These data show that, as with the
             nicotinic antagonist mecamylamine, there are significant
             interactions of dopamine systems with nicotine effects. ©
             1994 Wiley‐Liss, Inc. Copyright © 1994 Wiley‐Liss,
             Inc.},
   Doi = {10.1002/ddr.430310106},
   Key = {fds274332}
}

@article{fds274333,
   Author = {Levin, ED and Rosecrans, JA},
   Title = {Promise of nicotinic‐based therapeutic
             treatments},
   Journal = {Drug Development Research},
   Volume = {31},
   Number = {1},
   Pages = {1-2},
   Publisher = {WILEY},
   Year = {1994},
   Month = {January},
   ISSN = {0272-4391},
   url = {http://dx.doi.org/10.1002/ddr.430310102},
   Abstract = {Nicotine has a wide variety of pharmacological effects. Some
             of these, such as improved attentiveness and memory,
             quickened reaction time, reduced appetite, and lessening of
             stress can be viewed as beneficial and may partially
             underlie tobacco use. They also suggest therapeutic uses of
             nicotine. Like any drug, nicotine has adverse effects as
             well, such as convulsant actions and cardiovascular effects.
             Also, like a variety of therapeutic drugs from caffeine to
             codeine, nicotine has the adverse potential to become habit
             forming or addictive. Many of the health damaging effects of
             tobacco use, such as cancer and lung disease, seem to result
             from compounds present in tar. Eliminating the more than
             4,000 different compounds present in tar goes a long way in
             reducing adverse effects associated with nicotine intake.
             When developing nicotine for therapeutic use, it is critical
             to determine the mechanisms of its actions so that its
             beneficial effects can be maximized and its adverse effects
             can be minimized. This might be achieved with alternate
             routes of delivery of nicotine such as the skin patch or
             with novel nicotinic ligands currently under development. ©
             1994 Wiley‐Liss, Inc. Copyright © 1994 Wiley‐Liss,
             Inc.},
   Doi = {10.1002/ddr.430310102},
   Key = {fds274333}
}

@article{fds316112,
   Author = {MCEVOY, JP and ROSE, JE and LEVIN, ED and VANDERZWAAG, C and MCGEE,
             M},
   Title = {CLOZAPINE DECREASES DRIVE TO SMOKE},
   Journal = {Schizophrenia Research},
   Volume = {11},
   Number = {2},
   Pages = {104-104},
   Publisher = {ELSEVIER SCIENCE BV},
   Year = {1994},
   Month = {January},
   ISSN = {0920-9964},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:A1994MT53500041&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Key = {fds316112}
}

@article{fds136375,
   Title = {Levin ED and B Eisner. Nicotine interactions with dopamine
             agonists: Effects on working memory function. Drug
             Development Research, 31:32-37, 1994.},
   Year = {1994},
   Key = {fds136375}
}

@article{fds136376,
   Title = {Levin ED and J Rosecrans. The promise of nicotinic-based
             therapeutic treatments. Drug Development Research, 31:1-2,
             1994.},
   Year = {1994},
   Key = {fds136376}
}

@article{fds136377,
   Title = {Levin, ED. Nicotine effects and working memory performance.
             Recent Advances in Tobacco Science, 20:49-66,
             1994.},
   Year = {1994},
   Key = {fds136377}
}

@article{fds136378,
   Title = {AndrŽn PE, ED Levin, U Liminga and L Gunne. Behavioral and
             neurochemical consequences of ibotenic acid lesion in the
             subthalamic nucleus in the common marmoset. Brain Research
             Bulletin, 36:301-306, 1994.},
   Year = {1994},
   Key = {fds136378}
}

@article{fds136390,
   Title = {Levin ED, EC Westman, RM Stein, E Carnahan, M Sanchez, S
             Herman, FM Behm and JE Rose. Nicotine skin patch treatment
             increases abstinence, decreases withdrawal symptoms and
             attenuates rewarding effects of smoking. Journal of Clinical
             Psychopharmacology, 14:41-49, 1994.},
   Year = {1994},
   Key = {fds136390}
}

@article{fds136391,
   Title = {Brucato FH, ED Levin, JE Rose and HS Swartzwelder.
             Intracerebroventricular nicotine and mecamylamine alter
             radial-arm maze performance in rats. Drug Development
             Research, 31:18-23, 1994.},
   Year = {1994},
   Key = {fds136391}
}

@article{fds136392,
   Title = {Rose JE, FM Behm, EC Westman, ED Levin, RM Stein, J Lane and
             GV Ripka. Combined effects of nicotine and mecamylamine in
             attenuating smoking reward. Experimental and Clinical
             Psychopharmacology, 2:328-344, 1994.},
   Year = {1994},
   Key = {fds136392}
}

@article{fds274455,
   Author = {Levin, ED and Christopher, NC and Briggs, SJ and Rose,
             JE},
   Title = {Chronic nicotine reverses working memory deficits caused by
             lesions of the fimbria or medial basalocortical
             projection.},
   Journal = {Brain Research. Cognitive Brain Research},
   Volume = {1},
   Number = {3},
   Pages = {137-143},
   Year = {1993},
   Month = {October},
   ISSN = {0926-6410},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/8257869},
   Keywords = {Animals • Basal Ganglia • Cerebral Cortex •
             Choice Behavior • Denervation • Hippocampus •
             Male • Memory • Memory Disorders • Motor
             Activity • Nicotine • Rats • Rats,
             Sprague-Dawley • Reaction Time • Synaptic
             Transmission* • Time Factors • drug effects •
             pharmacology* • physiology • physiology* •
             psychology*},
   Abstract = {Nicotine has been found in a variety of studies to improve
             performance in memory tasks. This study was conducted to
             determine if chronic nicotine administration is useful in
             counteracting the working memory deficits seen after lesions
             of the fimbria or the medial basalocortical projection. Rats
             were trained to asymptotic performance on a working memory
             version of the radial-arm maze. Then, they were given knife
             cut lesions of the fimbria or the medial basalocortical
             projection or underwent sham surgeries. At the time of
             surgery, rats in each treatment group were implanted with
             either nicotine-containing or placebo glass and Silastic
             pellets. Rats with fimbria or basalocortical lesions showed
             a significant decline in working memory performance. Chronic
             nicotine significantly improved choice accuracy in both
             lesioned and unlesioned rats. Nicotine treatment restored
             performance of the lesioned rats to control levels. These
             data show that in addition to improving memory performance
             in normal rats, nicotine can counteract lesion-induced
             memory impairments. Nicotine also may be useful for
             treatment of disease-related memory impairments such as seen
             in Alzheimer's disease.},
   Doi = {10.1016/0926-6410(93)90021-v},
   Key = {fds274455}
}

@article{fds274512,
   Author = {Levin, ED and Behm, F and Carnahan, E and LeClair, R and Shipley, R and Rose, JE},
   Title = {Clinical trials using ascorbic acid aerosol to aid smoking
             cessation.},
   Journal = {Drug and Alcohol Dependence},
   Volume = {33},
   Number = {3},
   Pages = {211-223},
   Year = {1993},
   Month = {October},
   ISSN = {0376-8716},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/8261886},
   Keywords = {Adult • Aerosols • Ascorbic Acid • Equipment
             Design • Female • Humans • Male • Middle
             Aged • Nebulizers and Vaporizers* • Nicotine
             • Smoking Cessation • Substance Withdrawal
             Syndrome • administration & dosage* • adverse
             effects • etiology • methods*},
   Abstract = {Sensory aspects of cigarette smoke are important for
             providing smoking satisfaction. In previous studies, we have
             found that substitution of the sensory cues of smoking with
             a citric acid aerosol significantly reduces craving for
             cigarettes and enhances smoking reduction and cessation with
             people trying to quit smoking cigarettes. In the current
             study, we conducted two clinical smoking cessation trials
             using an ascorbic acid aerosol as a sensory substitute. The
             cigarette substitute consisted of a cigarette-sized tube
             which delivered a fine aerosol of ascorbic acid (approx. 1
             mg/puff, up to a maximum of 300 mg/day). Study 1 examined
             the overall effectiveness of the ascorbic acid smoking
             substitute device. One group of subjects which used the
             device and received clinical counseling was compared with
             another group which received only clinical counseling. The
             group using the device showed significantly greater
             abstinence rates at 3 weeks post-cessation. After the
             subjects stopped using the device, no difference in
             abstinence was detected. Study 2 was conducted to focus
             specifically on the role of tracheobronchial sensations in
             relieving craving for cigarettes. Two closely matched
             ascorbic acid delivery systems were compared. One device
             delivered fine particles of ascorbic acid that were targeted
             to reach the trachea, while the other delivered coarser
             particles of ascorbic acid that were not expected to reach
             the trachea or lower airways. An initial enhancement in
             smoking reduction was found for subjects using the fine
             particle device relative to those using the coarse particle
             device. However, by the end of treatment (5 weeks) both
             groups showed similar degrees of smoking reduction. For
             those who were abstinent from smoking at the end of
             treatment, craving for cigarettes and negative mood were
             both significantly lower for those using the fine particle
             device. Also, hunger for food was significantly lower in the
             fine particle device group. These results suggest that
             ascorbic acid delivered from a cigarette substitute may be
             effective in reducing smoking and promoting smoking
             abstinence.},
   Doi = {10.1016/0376-8716(93)90108-3},
   Key = {fds274512}
}

@article{fds274515,
   Author = {Rose, JE and Levin, ED and Benowitz, N},
   Title = {Saliva nicotine as an index of plasma levels in nicotine
             skin patch users.},
   Journal = {Therapeutic Drug Monitoring},
   Volume = {15},
   Number = {5},
   Pages = {431-435},
   Year = {1993},
   Month = {October},
   ISSN = {0163-4356},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/8249050},
   Keywords = {Administration, Cutaneous • Adult • Cotinine
             • Delayed-Action Preparations • Female •
             Humans • Hydrogen-Ion Concentration • Male •
             Middle Aged • Nicotine • Saliva •
             administration & dosage • analysis • analysis*
             • blood • blood* • chemistry*},
   Abstract = {This study examined whether salivary nicotine concentrations
             would provide a useful index of plasma concentrations in
             studies of the effects of transdermal nicotine
             administration. Twenty-four subject smokers abstained from
             smoking for 12 h prior to admission to a clinical research
             unit ward and for 36 h while remaining confined to the ward.
             Three doses of nicotine skin patches were applied to
             different groups of subjects, and blood and saliva samples
             were collected at several time points. Saliva flow was
             stimulated by three different methods: (a) sucking on a
             lemon candy, (b) dissolving a sugar cube in the mouth, and
             (c) chewing on parafilm. Nicotine and cotinine
             concentrations were measured in both saliva and blood using
             gas chromatography. There was a high correlation between
             blood and saliva values of nicotine (r = 0.82). Overall,
             saliva nicotine concentrations were approximately 8.1 times
             higher than those of plasma. Saliva and blood cotinine
             concentrations were also highly correlated (r = 0.94),
             replicating results of previous studies. Results suggest
             that saliva nicotine may be a useful marker of nicotine
             intake during nicotine skin patch treatment. Saliva
             collection may be advantageous under conditions in which
             blood collection is impractical and may provide greater
             sensitivity because of the high concentration of nicotine in
             saliva relative to that in blood.},
   Doi = {10.1097/00007691-199310000-00012},
   Key = {fds274515}
}

@article{fds274394,
   Author = {Westman, EC and Levin, ED and Rose, JE},
   Title = {The nicotine patch in smoking cessation. A randomized trial
             with telephone counseling.},
   Journal = {Archives of Internal Medicine},
   Volume = {153},
   Number = {16},
   Pages = {1917-1923},
   Year = {1993},
   Month = {August},
   ISSN = {0003-9926},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/8250653},
   Keywords = {Administration, Cutaneous • Adult • Counseling*
             • Delayed-Action Preparations • Double-Blind
             Method • Female • Follow-Up Studies • Humans
             • Male • Nicotine • Patient Compliance •
             Self-Help Groups • Smoking • Smoking Cessation*
             • Substance Withdrawal Syndrome • Telephone •
             administration & dosage* • adverse effects • drug
             therapy • physiopathology • psychology •
             therapeutic use},
   Abstract = {BACKGROUND: This study was conducted to determine the
             efficacy of the nicotine patch in smoking cessation when
             combined with self-help materials, three brief visits, and
             telephone counseling. METHODS: One hundred fifty-nine
             healthy volunteers who smoked at least one pack of
             cigarettes per day and desired to quit smoking were enrolled
             in a double-blind trial with 6-week treatment and 6-month
             follow-up periods. After review of self-help materials,
             subjects were randomly assigned to regimens of nicotine or
             placebo patches. Subjects wore two patches per day for 4
             weeks (25 mg of nicotine per 24 hours), then one patch per
             day for 2 weeks. Return visits were at the ends of weeks 4
             and 6. Telephone counseling was given during weeks 1, 2, 3,
             and 5. Abstinence at 6 weeks was defined as zero cigarettes
             smoked for the previous 28 days, verified by exhaled carbon
             monoxide less than 8 ppm at 4 weeks and 6 weeks. Abstinence
             at 3 and 6 months was defined as self-report of zero
             cigarettes since the previous contact, verified by carbon
             monoxide value at 6 months. RESULTS: Abstinence rates at 6
             weeks, 3 months, and 6 months were 29.5%, 21.8%, and 20.5%
             in the active group, and 8.8%, 3.8%, and 2.5% in the placebo
             group (P < or = .001 for each comparison), respectively.
             Skin irritation was the main side effect, causing 1.3% to
             drop out. CONCLUSION: The nicotine patch is efficacious in
             smoking cessation over a 6-month period, when combined with
             only self-help materials, three brief visits, and telephone
             counseling.},
   Doi = {10.1001/archinte.1993.00410160087008},
   Key = {fds274394}
}

@article{fds274475,
   Author = {Bushnell, PJ and Levin, ED},
   Title = {Effects of dopaminergic drugs on working and reference
             memory in rats.},
   Journal = {Pharmacology, Biochemistry, and Behavior},
   Volume = {45},
   Number = {4},
   Pages = {765-776},
   Year = {1993},
   Month = {August},
   ISSN = {0091-3057},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/8105486},
   Keywords = {(R)-2,3,4,5-Tetrahydro-8-chloro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol
             • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
             • Animals • Conditioning, Operant •
             Dextroamphetamine • Discrimination (Psychology) •
             Dopamine Agents • Ergolines • Male • Memory
             • Memory, Short-Term • Psychomotor Performance
             • Quinpirole • Raclopride • Rats •
             Receptors, Dopamine D2 • Salicylamides •
             antagonists & inhibitors • drug effects • drug
             effects* • pharmacology • pharmacology*},
   Abstract = {Changes in dopaminergic function have been associated with
             alterations in motor and cognitive function in man and in
             animals. This study was designed to assess the effects of
             dopaminergic drugs on these aspects of conditioned behavior
             in animals. Male Long-Evans rats were trained to perform an
             appetitive operant task that allowed daily quantification of
             working memory (accuracy of spatial delayed
             nonmatching-to-position), reference memory (accuracy of
             visual discrimination) and motor function [choice
             lever-press latency and nosepoke interresponse time (IRT)
             during delay]. The indirect dopamine agonist d-amphetamine
             (0.3-1.0 mg/kg) reduced nonmatching accuracy without
             significantly affecting discrimination accuracy, response
             latency, or nosepoke IRT. The D2/D3 agonist quinpirole
             (0.01-0.056 mg/kg) also decreased nonmatching accuracy
             without changing discrimination accuracy, but increased
             choice response latency and nosepoke IRT as well. The D1
             agonist SKF 38393 (1.0-3.0 mg/kg) and the D1 antagonist SCH
             23390 (0.01-0.03 mg/kg) only affected nosepoke IRT, at doses
             below those causing response failure. The D2 antagonist
             raclopride (0.056-0.177 mg/kg) exerted no significant
             effects at doses that did not suppress responding
             completely. The selective reduction of nonmatching accuracy
             by d-amphetamine and quinpirole indicates a mnemonic
             impairment specific to working memory (relative to reference
             memory). These results suggest further 1) that stimulation
             of D2/D3, but not D1, receptors may account for the
             d-amphetamine-induced deficit in working memory; 2) that
             stimulation of D2/D3 receptors alone by quinpirole may also
             impair spatial working memory, but only in conjunction with
             motor slowing; and 3) that antagonism of either receptor
             type (by SCH 23390 or raclopride) does not significantly
             affect memory at doses causing motor slowing and response
             failure.},
   Doi = {10.1016/0091-3057(93)90119-e},
   Key = {fds274475}
}

@article{fds274491,
   Author = {Levin, ED and Briggs, SJ and Christopher, NC and Rose,
             JE},
   Title = {Prenatal nicotine exposure and cognitive performance in
             rats.},
   Journal = {Neurotoxicology and Teratology},
   Volume = {15},
   Number = {4},
   Pages = {251-260},
   Year = {1993},
   Month = {July},
   ISSN = {0892-0362},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/8413079},
   Keywords = {Animals • Birth Weight • Body Weight •
             Cognition • Dose-Response Relationship, Drug •
             Female • Infusions, Intravenous • Learning •
             Male • Mecamylamine • Memory • Nicotine
             • Pregnancy • Prenatal Exposure Delayed Effects
             • Propranolol • Rats • Rats, Sprague-Dawley
             • Weight Gain • antagonists & inhibitors •
             drug effects • drug effects* • pharmacology •
             toxicity*},
   Abstract = {In humans and animal models there is evidence that prenatal
             nicotine exposure causes lasting deficits in cognitive
             performance. The current study examined the cognitive
             effects of prenatal exposure of rats to 2 mg/kg/day of
             nicotine. This dose did not cause significant deficits in
             maternal weight gain, offspring litter size, or pup weight.
             The control offspring showed the normal ontogeny of
             spontaneous alternation from near chance (50%) performance
             to 80%-85% alternation. In contrast, the nicotine-exposed
             rats had the opposite progression with abnormally high
             alternation on days 22-30 and abnormally low alternation on
             days 35-52. Acquisition of choice accuracy performance on
             the radial-arm maze (RAM) was not altered in a major way by
             nicotine exposure. Minor nicotine-induced changes in choice
             accuracy were seen during the initial trials of acquisition.
             The nicotine exposed female offspring had a significantly
             longer response duration. Prenatal nicotine exposure did
             significantly alter the effects of subsequent drug
             challenges on choice accuracy performance. The
             nicotine-exposed male offspring were significantly more
             responsive to the amnestic effects of the nicotinic
             antagonist mecamylamine. In a subsequent challenge, the
             effects of the beta-adrenergic antagonist propranolol were
             examined. A significant dose-related impairment in choice
             accuracy was seen in the control rats. In contrast, the
             nicotine-exposed rats did not show any significant response
             to propranolol. This decreased responsiveness to adrenergic
             challenge parallels the reduction in adrenergic response to
             nicotine challenge we previously found in littermates to the
             rats of the current study. Prenatal nicotine exposure causes
             subtle alterations in cognitive performance that can be
             magnified by challenges of nicotinic and adrenergic
             systems.},
   Doi = {10.1016/0892-0362(93)90006-a},
   Key = {fds274491}
}

@article{fds274353,
   Author = {Levin, ED},
   Title = {Development of treatments for toxicant-induced cognitive
             deficits.},
   Journal = {Neurotoxicology and Teratology},
   Volume = {15},
   Number = {3},
   Pages = {203-206},
   Year = {1993},
   Month = {May},
   ISSN = {0892-0362},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/8336681},
   Keywords = {Animals • Cognition Disorders • Humans •
             chemically induced* • drug therapy* •
             psychology},
   Abstract = {A wide variety of toxicants have been found to impair
             cognitive function. Some such as lead, organophosphate
             pesticides, and polychlorinated biphenyls are quite
             widespread in the environment. Others such as alcohol,
             nicotine, and cocaine are widely used drugs of abuse. Many
             people are chronically exposed to these toxicants. Lasting
             cognitive deficits can result, especially after
             developmental exposure. Considerable research has been
             directed at developing pharmacological agents to treat the
             cognitive dysfunction associated with Alzheimer's Disease,
             Unfortunately, other types of cognitive dysfunction, such as
             toxicant-induced cognitive deficits, have not received the
             same degree of attention, despite the fact that they are
             quite widespread and may be more amenable to development of
             useful therapeutic treatments. Animal models can be
             particularly useful because the agents causing these
             deficits are known. In addition, for a variety of neurotoxic
             compounds, information concerning the nature of the
             cognitive effect and mechanism of toxic action can help in
             development of treatments. Prevention of toxic exposure is
             ideal. Removal from the source of pollution after exposure
             can help, but for those who already carry the burden of
             persistent deficits, development of efficacious therapeutic
             treatments is a necessity.},
   Doi = {10.1016/0892-0362(93)90016-h},
   Key = {fds274353}
}

@article{fds274365,
   Author = {Rose, JE and Behm, FM and Levin, ED},
   Title = {Role of nicotine dose and sensory cues in the regulation of
             smoke intake.},
   Journal = {Pharmacology, Biochemistry, and Behavior},
   Volume = {44},
   Number = {4},
   Pages = {891-900},
   Year = {1993},
   Month = {April},
   ISSN = {0091-3057},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/8469698},
   Keywords = {Adult • Aerosols • Affect • Arousal •
             Carbon Monoxide • Cues* • Heart Rate • Humans
             • Male • Nicotine • Respiratory System •
             Smoking • Substance Withdrawal Syndrome •
             administration & dosage • analysis • drug effects
             • pharmacology* • physiopathology •
             psychology*},
   Abstract = {We investigated the role of nicotine dose and sensory cues
             in the regulation of ad lib smoke intake. The smoking
             behavior of 12 adult male smokers was assessed in three
             conditions, presenting either high-nicotine cigarette smoke
             (high nicotine, high sensory), diluted cigarette smoke (low
             nicotine, low sensory), or an aerosol containing cigarette
             smoke constituents suspended in solution, which was low in
             nicotine, yet high in sensory impact. Subjects showed marked
             compensatory increases in smoking with the dilute smoke
             conditions, whereas they puffed and inhaled the aerosol to a
             similar extent as the high-nicotine cigarette. Thus,
             subjects regulated their smoking behavior to equate sensory
             intensity rather than nicotine intake. Moreover, the aerosol
             and high-nicotine cigarette conditions lowered craving to a
             greater degree than the dilute smoke condition. Other mood
             indices, such as arousal and negative affect, were more
             effectively relieved by the high-nicotine dose condition.
             These results highlight the importance of sensory cues in
             the regulation of smoke intake and modulation of craving and
             suggest the clinical application of techniques for providing
             relief of cigarette craving during smoking
             cessation.},
   Doi = {10.1016/0091-3057(93)90021-k},
   Key = {fds274365}
}

@article{fds274429,
   Author = {Levin, ED and Briggs, SJ and Christopher, NC and Rose,
             JE},
   Title = {Chronic nicotinic stimulation and blockade effects on
             working memory.},
   Journal = {Behav Pharmacol},
   Volume = {4},
   Number = {2},
   Pages = {179-182},
   Year = {1993},
   Month = {April},
   ISSN = {0955-8810},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/11224184},
   Abstract = {Acute and chronic nicotine treatment has been found to
             improve learning and memory function in a variety of tasks.
             In several studies we have found that chronic nicotine
             infusion improves working memory performance. Replicating
             these results, the current study showed that chronic
             nicotine treatment (12mg/kg/day) significantly improved
             working memory performance in the radial-arm maze. The
             nicotine effect did not diminish during the 2 weeks
             following withdrawal. The nicotine-induced improvement was
             eliminated when the nicotinic antagonist mecamylamine
             (3mg/kg/day) was given concurrently, suggesting that the
             nicotine effect was mediated via actions on the nicotinic
             receptor. Surprisingly, when this chronic dose of
             mecamylamine was given alone, it caused a transient
             improvement in choice accuracy during the first week of
             administration. This improvement subsequently became
             attenuated and was not evident at all by the third and
             fourth weeks of administration.},
   Key = {fds274429}
}

@article{fds316115,
   Author = {WESTMAN, EC and LEVIN, ED and ROSE, JE},
   Title = {SMOKING WHILE WEARING THE NICOTINE PATCH - IS SMOKING STILL
             SATISFYING},
   Journal = {Clinical Research},
   Volume = {41},
   Number = {2},
   Pages = {A573-A573},
   Publisher = {SLACK INC},
   Year = {1993},
   Month = {April},
   ISSN = {0009-9279},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:A1993KW76102642&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Key = {fds316115}
}

@article{fds316100,
   Author = {WESTMAN, EC and SIMEL, DL and LEVIN, ED and ROSE,
             JE},
   Title = {PREDICTING SUCCESS OF THE NICOTINE PATCH IN SMOKING
             CESSATION USING BASE-LINE CLINICAL INFORMATION},
   Journal = {Clinical Research},
   Volume = {41},
   Number = {2},
   Pages = {A573-A573},
   Publisher = {SLACK INC},
   Year = {1993},
   Month = {April},
   ISSN = {0009-9279},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:A1993KW76102643&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Key = {fds316100}
}

@article{fds274415,
   Author = {Levin, ED and Briggs, SJ and Christopher, NC and Rose,
             JE},
   Title = {Sertraline attenuates hyperphagia in rats following nicotine
             withdrawal.},
   Journal = {Pharmacology, Biochemistry, and Behavior},
   Volume = {44},
   Number = {1},
   Pages = {51-61},
   Year = {1993},
   Month = {January},
   ISSN = {0091-3057},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/8430129},
   Keywords = {1-Naphthylamine • Animals • Body Weight •
             Dose-Response Relationship, Drug • Drinking Behavior
             • Eating • Female • Nicotine • Rats
             • Rats, Sprague-Dawley • Serotonin Uptake
             Inhibitors • Sertraline • Substance Withdrawal
             Syndrome • analogs & derivatives* • drug effects
             • drug effects* • pharmacology •
             pharmacology* • psychology*},
   Abstract = {Chronic nicotine administration can decrease food
             consumption and body weight. Abrupt withdrawal from nicotine
             can cause the reverse effect, hyperphagia and rapid weight
             gain. In the current study, the efficacy of sertraline, a
             serotonin reuptake inhibitor, on nicotine withdrawal-induced
             hyperphagia and rapid weight gain was assessed in rats.
             Sertraline was found to be effective in reversing the
             increase in feeding that occurred after withdrawal from
             chronic nicotine administration. Sertraline caused a
             dose-related decrease in food consumption in control rats
             not given nicotine. Doses of 5 and 10 mg/kg/day caused
             significant decreases while 2.5 mg/kg/day caused a slight
             though nonsignificant decrease in food consumption. Rats in
             which nicotine was abruptly withdrawn after 3 weeks of
             administration showed a significant increase in food
             consumption relative to controls. This increase was
             eliminated by the high dose of sertraline (10 mg/kg/day),
             but not by the lower two doses (2.5 and 5 mg/kg/day). Water
             consumption was affected in a similar fashion. Body weight
             gain was also affected by sertraline. During the first week
             after nicotine withdrawal, rats rapidly gained weight, but
             sertraline attenuated this. The 10-mg/kg dose of sertraline
             significantly attenuated the nicotine withdrawal-induced
             weight gain. These results suggest that sertraline can
             counteract the hyperphagia and rapid weight gain associated
             with nicotine withdrawal, and might therefore be a useful
             adjunct to smoking cessation.},
   Doi = {10.1016/0091-3057(93)90280-7},
   Key = {fds274415}
}

@article{fds274516,
   Author = {Behm, FM and Schur, C and Levin, ED and Tashkin, DP and Rose,
             JE},
   Title = {Clinical evaluation of a citric acid inhaler for smoking
             cessation.},
   Journal = {Drug and Alcohol Dependence},
   Volume = {31},
   Number = {2},
   Pages = {131-138},
   Year = {1993},
   Month = {January},
   ISSN = {0376-8716},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/8436059},
   Keywords = {Adult • Aerosols • Affect • Behavior Therapy
             • Breath Tests • Carbon Monoxide • Citrates
             • Citric Acid • Double-Blind Method •
             Equipment Design • Female • Humans • Male
             • Middle Aged • Nebulizers and Vaporizers* •
             Nicotine • Smoking Cessation • Substance
             Withdrawal Syndrome • administration & dosage* •
             adverse effects • blood • drug effects •
             methods* • prevention & control},
   Abstract = {In this study, we evaluated the efficacy of a hand-held
             inhaler as an adjunct to a smoking cessation behavioral
             program. The inhaler delivered a citric acid aerosol with
             tobacco smoke flavor. Seventy-four smokers were recruited
             for a 3-week smoking cessation trial. During the first 12
             days of the cessation period, smokers used the citric acid
             aerosol inhaler instead of a cigarette whenever the urge to
             smoke occurred. The citric acid inhaler significantly
             reduced CO levels and enhanced rates of smoking abstinence
             for those with higher than average (34.2 ppm) baseline
             end-expired carbon monoxide (CO) levels. Craving for
             cigarettes and negative affect were also alleviated by the
             citric acid aerosol. These results suggest that the citric
             acid aerosol may promote successful smoking reduction or
             cessation in a subgroup of smokers and relieves withdrawal
             symptoms such as craving for cigarettes, a symptom difficult
             to treat with currently available nicotine replacement
             techniques.},
   Doi = {10.1016/0376-8716(93)90065-x},
   Key = {fds274516}
}

@article{fds274502,
   Author = {Levin, ED and Seidler, FJ},
   Title = {Sex-related spatial learning differences after prenatal
             cocaine exposure in the young adult rat.},
   Journal = {Neurotoxicology},
   Volume = {14},
   Number = {1},
   Pages = {23-28},
   Year = {1993},
   ISSN = {0161-813X},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/8361675},
   Keywords = {Animals • Choice Behavior • Cocaine • Drug
             Interactions • Female • Learning • Male
             • Pregnancy • Prenatal Exposure Delayed Effects*
             • Rats • Rats, Sprague-Dawley • Receptors,
             Cholinergic • Scopolamine • Sex Characteristics*
             • Spatial Behavior* • drug effects • drug
             effects* • pharmacology • toxicity*},
   Abstract = {Prenatal cocaine exposure in humans is associated with a
             variety of adverse neurobehavioral effects. In the rat, in
             utero cocaine exposure has been shown to elicit learning
             impairment during early postnatal development. However,
             little research has focused on the persistence of these
             behavioral disruptions. The current study examines the
             long-term effects of prenatal cocaine exposure on learning
             performance during young adulthood. Fetal cocaine exposure
             evoked differential effects in male and female rats on
             radial-arm maze learning performance. Cocaine-treated
             females showed significantly impaired choice accuracy during
             acquisition of radial-arm maze performance when compared to
             control females. In contrast, cocaine-treated males showed
             no impairment and in fact showed significantly improved
             performance on one measure of choice accuracy. For both
             sexes, this effect was apparent during the final third of
             acquisition. No evidence was found to suggest altered
             sensitivity to anticholinergic drugs. While both nicotinic
             and muscarinic cholinergic antagonists caused significant
             impairments in memory performance, control and
             cocaine-exposed rats were effected equally. Single doses of
             these drugs which caused moderate memory deficits were
             chosen for use in the current study. The entire dose range
             should be evaluated to determine the relative sensitivity of
             cocaine-exposed and control animals to these drugs. The
             results of this study indicate that there are cognitive
             effects of prenatal cocaine exposure which persist into
             adulthood and the sex of the offspring seems to be
             critical.},
   Key = {fds274502}
}

@article{fds316097,
   Author = {WESTMAN, EC and LEVIN, ED and ROSE, JE},
   Title = {SMOKING WHILE WEARING THE NICOTINE PATCH - IS SMOKING
             SATISFYING OR HARMFUL},
   Journal = {Clinical Research},
   Volume = {40},
   Number = {4},
   Pages = {A871-A871},
   Publisher = {SLACK INC},
   Year = {1992},
   Month = {December},
   ISSN = {0009-9279},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:A1992KE14100534&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Key = {fds316097}
}

@article{fds316098,
   Author = {WESTMAN, EC and SIMEL, DL and LEVIN, ED and ROSE,
             JE},
   Title = {DERIVATION OF A LOGISTIC MODEL USING BASE-LINE CLINICAL
             INFORMATION TO PREDICT SUCCESS WITH THE NICOTINE PATCH IN
             SMOKING CESSATION},
   Journal = {Clinical Research},
   Volume = {40},
   Number = {4},
   Pages = {A811-A811},
   Publisher = {SLACK INC},
   Year = {1992},
   Month = {December},
   ISSN = {0009-9279},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:A1992KE14100218&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Key = {fds316098}
}

@article{fds274468,
   Author = {Seidler, FJ and Levin, ED and Lappi, SE and Slotkin,
             TA},
   Title = {Fetal nicotine exposure ablates the ability of postnatal
             nicotine challenge to release norepinephrine from rat brain
             regions.},
   Journal = {Brain Research. Developmental Brain Research},
   Volume = {69},
   Number = {2},
   Pages = {288-291},
   Year = {1992},
   Month = {October},
   ISSN = {0165-3806},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/1424104},
   Keywords = {Animals • Brain • Cerebral Cortex • Female
             • Fetus • Hippocampus • Infusions, Parenteral
             • Injections, Subcutaneous • Male •
             Maternal-Fetal Exchange • Mesencephalon •
             Methyltyrosines • Nicotine • Norepinephrine •
             Pregnancy • Rats • Rats, Sprague-Dawley •
             administration & dosage • alpha-Methyltyrosine •
             drug effects • drug effects* • metabolism •
             metabolism* • pharmacology • pharmacology*},
   Abstract = {Exposure of the fetus to nicotine is known to affect the
             function of noradrenergic pathways in the central nervous
             system. In the current study, synaptic mechanisms underlying
             the functional defects were evaluated in the offspring of
             pregnant rats given nicotine infusions of 2 mg/kg/day
             throughout gestation, administered by osmotic minipumps. At
             30 days postpartum, norepinephrine levels in brain regions
             of the offspring were significantly reduced. More
             importantly, acute challenge with either 0.1 mg/kg or 0.3
             mg/kg of nicotine evoked significant norepinephrine release
             from brain regions of control animals, but failed to do so
             in the fetal nicotine cohort. These results suggest that
             prenatal exposure to nicotine produces a deficit in
             subsequent noradrenergic responsiveness, deficits which may
             participate in behavioral and neuroendocrine
             abnormalities.},
   Doi = {10.1016/0165-3806(92)90170-2},
   Key = {fds274468}
}

@article{fds274389,
   Author = {Uemura, E and Levin, ED},
   Title = {The effect of halothane on cultured fibroblasts and
             neuroblastoma cells.},
   Journal = {Neuroscience Letters},
   Volume = {145},
   Number = {1},
   Pages = {33-36},
   Year = {1992},
   Month = {September},
   ISSN = {0304-3940},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/1461563},
   Keywords = {Actins • Animals • Cells, Cultured • Female
             • Fibroblasts • Halothane • Mice •
             Microtubules • Nervous System Neoplasms •
             Neuroblastoma • Pregnancy • Rats • Rats,
             Sprague-Dawley • Tumor Cells, Cultured •
             biosynthesis • drug effects • metabolism* •
             pharmacology*},
   Abstract = {Halothane exposure over the cultured cells (100 and 1,000
             ppm) caused a disruption of the pattern of actin
             distribution in both fibroblasts and neuroblastoma cells.
             Neuroblastoma cells exposed to halothane also lost
             microspikes; however, neurite elongation was not affected by
             halothane. The present study suggests that halothane induces
             the functional disruption of actin, resulting in an
             interference of normal neural development in
             vivo.},
   Doi = {10.1016/0304-3940(92)90196-e},
   Key = {fds274389}
}

@article{fds274396,
   Author = {Levin, ED and Briggs, SJ and Christopher, NC and Rose,
             JE},
   Title = {Persistence of chronic nicotine-induced cognitive
             facilitation.},
   Journal = {Behavioral and Neural Biology},
   Volume = {58},
   Number = {2},
   Pages = {152-158},
   Year = {1992},
   Month = {September},
   ISSN = {0163-1047},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/1456935},
   Keywords = {Analysis of Variance • Animals • Cognition •
             Learning • Male • Memory • Nicotine •
             Rats • Rats, Sprague-Dawley • Task Performance and
             Analysis • Time Factors • drug effects • drug
             effects* • pharmacology*},
   Abstract = {Nicotine has been found in a variety of species and
             behavioral paradigms to improve memory performance. The
             beneficial effect of nicotine has been seen after both acute
             and chronic administration. Interestingly, improved
             performance has been seen 24 h after acute injection and for
             at least 2 weeks after chronic administration. However, it
             is not clear from previous studies whether the persistence
             of the improved performance represents a true carryover of
             the drug effect or is due to the behavioral experience while
             under nicotine's effect. The current study was conducted to
             determine whether the facilitating effect of nicotine on
             learning and memory performance could be seen after
             withdrawal even if there was no behavioral training during
             the period of chronic nicotine administration. Rats were
             administered nicotine chronically for 3 weeks but were not
             tested during that time. Starting 1 week after withdrawal
             they were trained on a working memory paradigm in an
             eight-arm radial maze. The nicotine-treated rats started out
             at control-like levels of performance, but showed
             significantly faster learning as detected by three different
             measures of choice accuracy. By the final phase of testing
             the control subjects had caught up with the nicotine-treated
             rats. After the acquisition phase, acute challenges with the
             nicotinic and muscarinic antagonists, mecamylamine and
             scopolamine, did not elicit any differential effects in the
             nicotine-treated and control groups. The current study
             demonstrated that nicotine-induced cognitive facilitation
             persists for at least 4 weeks after withdrawal and does not
             depend upon behavioral test experience under the influence
             of the drug. The mechanism for this persisting effect is not
             currently understood.(ABSTRACT TRUNCATED AT 250
             WORDS)},
   Doi = {10.1016/0163-1047(92)90399-o},
   Key = {fds274396}
}

@article{fds274449,
   Author = {McGurk, SR and Levin, ED and Butcher, LL},
   Title = {Dopaminergic drugs reverse the impairment of radial-arm maze
             performance caused by lesions involving the cholinergic
             medial pathway.},
   Journal = {Neuroscience},
   Volume = {50},
   Number = {1},
   Pages = {129-135},
   Year = {1992},
   Month = {September},
   ISSN = {0306-4522},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/1357591},
   Keywords = {(R)-2,3,4,5-Tetrahydro-8-chloro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol
             • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
             • Acetylcholine • Animals • Cerebral Cortex
             • Dopamine Agents • Dopamine Antagonists •
             Ergolines • Female • Learning • Memory •
             Quinpirole • Raclopride • Rats • Rats,
             Sprague-Dawley • Receptors, Dopamine D1 •
             Receptors, Dopamine D2 • Salicylamides •
             Stereotaxic Techniques • drug effects • drug
             effects* • pharmacology • pharmacology* •
             physiology • physiology*},
   Abstract = {Pharmacological studies have shown that both cholinergic and
             dopaminergic transmitter systems are crucial for optimal
             choice accuracy in the radial-arm maze and that these
             systems interact in a complex fashion. Lesion studies have
             provided evidence that the basal nuclear complex of the
             forebrain, the origin of cholinergic projections to the
             cerebral mantle, may be critical for the cholinergic
             modulation of learning and memory. We have shown that
             knife-cut lesions of the medial cholinergic pathway
             significantly impair radial-arm maze choice accuracy
             performance. The current study examined the effectiveness of
             D1 and D2 ligands in counteracting this lesion-induced
             deficit. The adverse effects of medial cholinergic pathway
             lesions were diminished or reversed by daily treatment with
             a D1 agonist (SKF 38393), a D2 agonist (LY 171555) or a D1
             antagonist (SCH 23390), but were not affected by treatment
             with a D2 antagonist (raclopride). The three beneficial
             treatments have previously been found to attenuate the
             adverse effects of nictonic or muscarinic blockade on choice
             accuracy performance in the radial-arm maze. The finding
             that these dopaminergic drugs ameliorate the memory deficit
             caused by lesions involving the cholinergic medial pathway
             suggests the importance of interactions between cholinergic
             and dopaminergic systems in radial-arm maze performance.
             These results may provide leads for the development of novel
             therapeutic approaches for treating human disorders thought
             to result from cholinergic hypofunction.},
   Doi = {10.1016/0306-4522(92)90387-h},
   Key = {fds274449}
}

@article{fds274462,
   Author = {Levin, ED and Schantz, SL and Bowman, RE},
   Title = {Use of the lesion model for examining toxicant effects on
             cognitive behavior.},
   Journal = {Neurotoxicology and Teratology},
   Volume = {14},
   Number = {2},
   Pages = {131-141},
   Year = {1992},
   Month = {March},
   ISSN = {0892-0362},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/1593987},
   Keywords = {Aging • Animals • Aroclors • Brain •
             Cognition • Discrimination (Psychology) •
             Haplorhini • Lead • Lead Poisoning • Learning
             • Memory • Organ Specificity • drug effects
             • drug effects* • growth & development •
             pathology • physiology* • physiopathology* •
             toxicity*},
   Abstract = {It is often beneficial to use a model to help understand
             unknown effects and relate those effects to an existing body
             of knowledge. In much of the early development of behavioral
             toxicology, the pharmacological model has served as a
             valuable theoretical guide, especially with regard to dosing
             and kinetic parameters. However, as with any model, it has
             certain limitations. The lesion model has complementary
             features which provide valuable insights into the behavioral
             effects of toxicants. This is particularly true for effects
             which persist long after the end of toxicant exposure. There
             is much literature describing effects of brain lesions on
             behavior. By comparing results from toxicology studies to
             those of lesion studies, one can take advantage of this
             trove of information to gain a better insight into the
             possible loci of toxic effects, and to identify tests which
             would be useful in further describing the nature of the
             toxic effects. In this article, we examine the theoretical
             and practical utility of the lesion model. Examples are
             given showing how it has proven useful in interpreting the
             cognitive effects of exposure of monkeys to lead and
             polychlorinated biphenyls (PCBs). These exposures produced
             syndromes that closely resemble the effects of lesions in
             the frontal cortex or limbic system.},
   Doi = {10.1016/0892-0362(92)90061-e},
   Key = {fds274462}
}

@article{fds274208,
   Author = {Levin, E and Schantz, SL and Bowman, RE},
   Title = {Erratum: Use of the lesion model for examining toxicant
             effects on cognitive behavior (Neurotoxicol. Teratol. 14
             (131-142) 1992)},
   Journal = {Neurotoxicology and Teratology},
   Volume = {14},
   Number = {4},
   Pages = {298},
   Publisher = {Elsevier BV},
   Year = {1992},
   Month = {January},
   ISSN = {0892-0362},
   url = {http://dx.doi.org/10.1016/0892-0362(92)90010-8},
   Doi = {10.1016/0892-0362(92)90010-8},
   Key = {fds274208}
}

@article{fds274346,
   Author = {Rose, JE and Levin, ED},
   Title = {Concurrent agonist-antagonist administration for the
             analysis and treatment of drug dependence.},
   Journal = {Pharmacology, Biochemistry, and Behavior},
   Volume = {41},
   Number = {1},
   Pages = {219-226},
   Year = {1992},
   Month = {January},
   ISSN = {0091-3057},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/1539072},
   Keywords = {Animals • Drug Antagonism* • Humans •
             Substance-Related Disorders • drug therapy*},
   Abstract = {Two key strategies for the treatment of drug dependence
             involve the use of agonists to substitute for the abused
             drug and the use of antagonists to block the reinforcing
             actions maintaining drug self-administration. A different
             strategy for the treatment of drug dependence is outlined,
             comprising the concurrent administration of an agonist and
             an antagonist. Concurrent administration of an agonist with
             an antagonist, in the proper ratio, should produce maximal
             occupancy of receptors and attenuation of the reinforcing
             actions of the abused drug. The addict would be relatively
             "insulated" from the reinforcing effects of the abused drug;
             at the same time the balance of agonist and antagonist
             effects is predicted to prevent withdrawal symptoms or
             intoxication resulting from an under- or over-stimulation of
             drug receptors. Advantages over the use of agonists alone
             and antagonists alone, and over mixed agonist-antagonist
             molecules, are discussed. Application of concurrent
             agonist-antagonist administration to the analysis of
             mechanisms underlying nondrug reinforcement and to the
             treatment of disorders involving receptor disregulation is
             also described.},
   Doi = {10.1016/0091-3057(92)90086-u},
   Key = {fds274346}
}

@article{fds316081,
   Author = {LEVIN, ED},
   Title = {ANIMAL-MODELS OF NICOTINE EFFECTS ON WEIGHT
             REGULATION},
   Journal = {Health Psychology : Official Journal of the Division of
             Health Psychology, American Psychological
             Association},
   Volume = {11},
   Pages = {40-40},
   Publisher = {AMER PSYCHOLOGICAL ASSOC},
   Year = {1992},
   Month = {January},
   ISSN = {0278-6133},
   url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:A1992JK24600012&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
   Key = {fds316081}
}

@article{fds274359,
   Author = {Henningfield, JE and Obarzanek, E and Benowitz, NL and Hall, SM and Klesges, RC and Leischow, S and Levin, ED and Perkins, KA and Spring, B and Stitzer, M},
   Title = {National working conference on smoking and body weight. Task
             Force 2: Methods of assessment, strategies for
             research.},
   Journal = {Health Psychology : Official Journal of the Division of
             Health Psychology, American Psychological
             Association},
   Volume = {11 Suppl},
   Pages = {10-16},
   Year = {1992},
   ISSN = {0278-6133},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/1396498},
   Keywords = {Adipose Tissue • Adult • Animals • Body Mass
             Index • Body Weight* • Energy Metabolism •
             Exertion • Feeding Behavior • Female • Humans
             • Male • Nicotine • Research Design •
             Smoking • administration & dosage • metabolism
             • psychology*},
   Key = {fds274359}
}

@article{fds274423,
   Author = {Levin, ED},
   Title = {Nicotinic systems and cognitive function.},
   Journal = {Psychopharmacology},
   Volume = {108},
   Number = {4},
   Pages = {417-431},
   Year = {1992},
   ISSN = {0033-3158},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/1357713},
   Keywords = {Animals • Behavior, Animal • Cognition •
             Cognition Disorders • Humans • Neurotransmitter
             Agents • Nicotine • Receptors, Muscarinic •
             Receptors, Nicotinic • drug effects • drug therapy
             • pharmacology* • physiology • physiology*
             • therapeutic use},
   Abstract = {Nicotinic acetylcholine receptors have been found to be
             important for maintaining optimal performance on a variety
             of cognitive tasks. In humans, nicotine-induced improvement
             of rapid information processing is particularly well
             documented. In experimental animals nicotine has been found
             to improve learning and memory on a variety of tasks, while
             the nicotinic antagonist mecamylamine has been found to
             impair memory performance. Nicotine has been found to be
             effective in attenuating memory deficits resulting from
             lesions of the septohippocampal pathway or aging in
             experimental animals. Nicotinic receptors are decreased in
             the cortex of patients with Alzheimer's disease. Preliminary
             studies have found that some aspects of the cognitive
             deficit in Alzheimer's disease can be attenuated by
             nicotine. Nicotine may prove to be useful therapeutic
             treatment for this and other types of dementia.},
   Doi = {10.1007/bf02247415},
   Key = {fds274423}
}

@article{fds274369,
   Author = {Levin, ED and Uemura, E and Bowman, RE},
   Title = {Neurobehavioral toxicology of halothane in
             rats.},
   Journal = {Neurotoxicology and Teratology},
   Volume = {13},
   Number = {4},
   Pages = {461-470},
   Year = {1991},
   Month = {July},
   ISSN = {0892-0362},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/1921926},
   Keywords = {Animals • Behavior, Animal • Discrimination
             Learning • Exploratory Behavior • Halothane •
             Nervous System • Rats • Spatial Behavior •
             drug effects • drug effects* • pathology •
             toxicity*},
   Abstract = {Halothane, a commonly used general anesthetic, is considered
             to be relatively safe for that purpose. Chronic exposure,
             however, has been found to cause long-lasting damage to
             neural structure and impairment of behavioral function. In
             rats, behavioral alterations are particularly evident after
             developmental exposure, but they can also be seen with adult
             exposure, especially when halothane is given during the
             period of neural regrowth following a brain lesion. The
             pattern of neural damage includes retarded synaptogenesis,
             impaired dendritic branching and disruption of organelle
             structure. The behavioral syndrome includes learning
             impairment, decreased exploratory behavior and decreased
             nociceptive reactivity. In general, the neural pathology is
             more pronounced and more easily discernible than the
             behavioral effects. Neural damage, particularly to the
             hippocampus, can be clearly seen at points when behavioral
             impairments have not been found. This demonstrates that in
             some cases changes in neural structure can be more sensitive
             indicators of toxic damage than behavioral dysfunction.
             Halothane exposure has proved to be quite useful as an
             experimental tool in the study of neural and behavioral
             recovery after brain lesions. For example, after unilateral
             entorhinal cortical lesions, behavioral recovery and
             reactive synaptogenesis occur contemporaneously. It has not
             been demonstrated whether the behavioral recovery is due to
             this reinnervation. Postlesion halothane exposure almost
             completely suppresses reactive synaptogenesis, however,
             behavioral recovery of T-maze alternation behavior occurs in
             the halothane-treated rats as well as in controls. This
             suggests that recovery of spatial performance after such a
             lesion is not due to recovery of innervation in the dentate,
             but to some other process such as other neural systems
             taking over the functions lost with the brain lesion. The
             studies reviewed highlight the dangers of halothane
             exposure, especially during development or when recovering
             from brain injury. They also provide a good case study for
             comparing the relative sensitivity of morphological and
             behavioral measures in toxicology and point to the potential
             use of halothane as an experimental tool for examining the
             relationships between neural structure and behavioral
             function.},
   Doi = {10.1016/0892-0362(91)90096-f},
   Key = {fds274369}
}

@article{fds274471,
   Author = {Levin, ED and Rose, JE},
   Title = {Nicotinic and muscarinic interactions and choice accuracy in
             the radial-arm maze.},
   Journal = {Brain Research Bulletin},
   Volume = {27},
   Number = {1},
   Pages = {125-128},
   Year = {1991},
   Month = {July},
   ISSN = {0361-9230},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/1933424},
   Keywords = {Animals • Choice Behavior • Drug Interactions
             • Female • Learning • Mecamylamine •
             Memory • Nicotine • Pilocarpine • Rats •
             Rats, Inbred Strains • Reference Values •
             Scopolamine • drug effects* • pharmacology*},
   Abstract = {Muscarinic acetylcholine (ACh) systems have long been known
             to be necessary for accurate performance in cognitive tests.
             Nicotinic ACh systems have been shown to be involved as
             well. However, there is only a limited amount of information
             concerning the interactions of these two branches of the ACh
             transmitter system. The current study was conducted to
             investigate the improvement in choice accuracy caused by
             muscarinic and nicotinic agonists and how it is affected by
             antagonists of these systems. Adult female Sprague-Dawley
             strain rats (N = 11) were trained on a working memory task
             in an 8-arm radial maze. Acute injections of the muscarinic
             and nicotinic agonists, pilocarpine (PILO, 1.0 mg/kg) and
             nicotine (NIC, 0.2 mg/kg), were made alone or in combination
             with the muscarinic and nicotinic antagonists, scopolamine
             (SCOP, 0.1 mg/kg) and mecamylamine (MEC, 10 mg/kg). NIC
             administration caused a significant improvement in choice
             accuracy compared with saline (p less than 0.01) and PILO
             caused a marginally significant improvement in choice
             accuracy (p less than 0.06). The combination of these
             nicotinic and muscarinic agonists did not cause an additive
             improvement. However, the improvement caused by either
             agonist was reversed by both nicotinic or muscarinic
             antagonists. This reversal was more complete for NIC than
             PILO despite the fact that NIC caused a greater improvement
             than PILO. These results suggest that muscarinic and
             nicotinic components of the ACh system, which are both
             important for cognitive function, interact in important
             ways. These interactions may be critical to consider when
             devising treatments for cognitive dysfunction associated
             with cholinergic hypofunction such as with Alzheimer's
             disease.},
   Doi = {10.1016/0361-9230(91)90293-s},
   Key = {fds274471}
}

@article{fds274477,
   Author = {Levin, ED and Rose, JE and Behm, F and Caskey, NH},
   Title = {The effects of smoking-related sensory cues on psychological
             stress.},
   Journal = {Pharmacology, Biochemistry, and Behavior},
   Volume = {39},
   Number = {2},
   Pages = {265-268},
   Year = {1991},
   Month = {June},
   ISSN = {0091-3057},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/1946567},
   Keywords = {Adolescent • Adult • Affect • Anxiety •
             Cues* • Female • Humans • Male • Middle
             Aged • Smoking • Stress, Psychological • drug
             effects • psychology • psychology*},
   Abstract = {Previous studies have shown that the sensory cues of
             cigarette smoking are important for smoking satisfaction and
             craving reduction. Sensory cues in the absence of
             pharmacological doses of nicotine have been found to be
             moderately satisfying and to reduce craving. The current
             study was conducted to determine if administration of the
             sensory cues of cigarette smoking with minimal nicotine
             would also provide relief from mild anxiety associated with
             anticipation of a difficult anagram test. This test has
             previously been shown to be sensitive to the anxiety
             relieving effects of cigarette smoking. Compared to the
             placebo control condition, the sensory condition caused a
             significant alleviation of the stress as measured by
             components of the Spielberger scale for anxiety. The
             addition of cigarette smoke containing 0.5 mg of nicotine to
             the sensory cues caused a slight though nonsignificant
             enhancement of the stress alleviation. These results
             demonstrate that sensory cues of smoking can provide similar
             effects as nicotine containing cigarettes with regard to
             stress alleviation. Previous studies had shown that sensory
             cues are important for the consumptive aspects of smoking
             (i.e., smoking satisfaction and craving reduction). The
             current study shows that sensory cues are important for
             other effects of smoking as well.},
   Doi = {10.1016/0091-3057(91)90177-4},
   Key = {fds274477}
}

@article{fds274417,
   Author = {Rose, JE and Levin, ED},
   Title = {Inter-relationships between conditioned and primary
             reinforcement in the maintenance of cigarette
             smoking.},
   Journal = {British Journal of Addiction},
   Volume = {86},
   Number = {5},
   Pages = {605-609},
   Year = {1991},
   Month = {May},
   ISSN = {0952-0481},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/1859927},
   Keywords = {Arousal • Association Learning • Brain •
             Conditioning, Classical • Extinction, Psychological
             • Humans • Nicotine • Recurrence •
             Smoking • Substance Withdrawal Syndrome •
             administration & dosage • adverse effects* • drug
             effects • drug effects* • prevention & control
             • psychology* • therapy},
   Abstract = {Research on smoking cessation has increasingly focussed on
             pharmacological aspects of nicotine and nicotine withdrawal.
             However, cigarette smoking also provides a characteristic
             set of sensory cues. These sensory aspects of smoking are
             important to address in that they may be potent conditioned
             reinforcing stimuli linked to the actions of nicotine. The
             repetition of the smoking act thousands of times per year by
             a moderately heavy smoker leads to a strong conditioned
             association between the sensory aspects of smoking (the
             putative CS) and the pharmacological effects of nicotine
             (the putative UCS). Strategies for disrupting CS-UCS
             associations may be useful in developing more effective
             smoking cessation treatments. These include:
             counterconditioning of the CS; presenting the CS alone;
             presenting the CS with the UCS but pharmacologically
             blocking the UCS; and presenting the CS and UCS in an
             unconnected fashion. The role of sensory cues in alleviating
             craving for cigarettes is discussed, and specific techniques
             for duplicating relevant sensory aspects of smoking without
             delivering significant doses of nicotine are described. The
             combination of nicotine and nicotinic antagonists to block
             primary reinforcement and hasten extinction of conditioned
             reinforcement is also considered.},
   Doi = {10.1111/j.1360-0443.1991.tb01816.x},
   Key = {fds274417}
}

@article{fds274495,
   Author = {Levin, ED and Rose, JE},
   Title = {Interactive effects of D1 and D2 agonists with scopolamine
             on radial-arm maze performance.},
   Journal = {Pharmacology, Biochemistry, and Behavior},
   Volume = {38},
   Number = {2},
   Pages = {243-246},
   Year = {1991},
   Month = {February},
   ISSN = {0091-3057},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/1676165},
   Keywords = {2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
             • Animals • Cognition • Dopamine Agents
             • Dose-Response Relationship, Drug • Ergolines
             • Exploratory Behavior • Female • Haloperidol
             • Quinpirole • Rats • Rats, Inbred Strains
             • Receptors, Dopamine • Receptors, Dopamine D1
             • Receptors, Dopamine D2 • Scopolamine • drug
             effects • drug effects* • pharmacology •
             pharmacology* • physiology*},
   Abstract = {Pharmacological blockade of muscarinic cholinergic (ACh)
             receptors has been found to impair choice accuracy in a
             variety of tasks including the radial-arm maze. The
             cognitive impairment caused by the muscarinic antagonist
             scopolamine is reversed by the dopaminergic (DA) antagonist
             haloperidol as well as the selective D1 antagonist SCH
             23390. In the current study, interactions were studied
             between scopolamine and selective agonists of D1 (SCH 38393)
             and D2 (quinpirole) receptors. Surprisingly, the D1 agonist
             SKF 38393 was found to significantly alleviate the
             scopolamine-induced choice accuracy deficit. In contrast,
             the D2 agonist quinpirole was not found to significantly
             alter the effects of scopolamine on choice accuracy but did
             have supra-additive effects of increasing choice latency.
             Both the D1 agonist SKF 38393 and the D1 antagonist SCH
             23390 have been found to reverse the choice accuracy deficit
             caused by scopolamine and the deficit resulting from lesions
             of the medial projection from the basal forebrain to the
             cortex. Possible mechanisms for these effects are
             discussed.},
   Doi = {10.1016/0091-3057(91)90272-4},
   Key = {fds274495}
}

@article{fds274207,
   Author = {Schantz, SL and Levin, ED and Bowman, RE},
   Title = {Long‐term neurobehavioral effects of perinatal
             polychlorinated biphenyl (PCB) exposure in
             monkeys},
   Journal = {Environmental Toxicology and Chemistry},
   Volume = {10},
   Number = {6},
   Pages = {747-756},
   Publisher = {WILEY},
   Year = {1991},
   Month = {January},
   ISSN = {0730-7268},
   url = {http://dx.doi.org/10.1002/etc.5620100606},
   Abstract = {In recent years, there has been growing concern about the
             potential long‐term neurobe‐havioral effects of
             perinatal polychlorinated biphenyl (PCB) exposure. We have
             addressed this issue in a series of studies at the Harlow
             Primate Laboratory. Offspring of rhesus monkeys (Macaca
             mulatto) exposed to commercial PCB mixtures (Aroclor 1016 or
             Aroclor 1248) were tested on two‐choice
             discrimination‐reversal learning at 1.5 years of age and
             on delayed spatial alternation, a spatial learning and
             memory task, at four to six years of age. Deficits in
             performance were observed on both tasks. The deficit
             observed on delayed spatial alternation in Aroclor
             1248‐exposed monkeys was quite dramatic. The monkeys were
             tested for 80 test sessions, but were never able to achieve
             control levels of performance. This effect was observed when
             the monkeys were four to six years of age (young adulthood),
             even though they had not been exposed to PCBs since they
             were weaned at four months of age. The pattern of effects on
             both discrimination‐reversal learning and delayed spatial
             alternation was suggestive of damage to the prefrontal
             cortex. Copyright © 1991 SETAC},
   Doi = {10.1002/etc.5620100606},
   Key = {fds274207}
}

@article{fds274487,
   Author = {McGurk, SR and Levin, ED and Butcher, LL},
   Title = {Impairment of radial-arm maze performance in rats following
             lesions involving the cholinergic medial pathway: reversal
             by arecoline and differential effects of muscarinic and
             nicotinic antagonists.},
   Journal = {Neuroscience},
   Volume = {44},
   Number = {1},
   Pages = {137-147},
   Year = {1991},
   ISSN = {0306-4522},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/1770993},
   Keywords = {Animals • Arecoline • Caudate Nucleus •
             Cholinergic Fibers • Female • Learning •
             Mecamylamine • Memory • Nerve Regeneration •
             Putamen • Rats • Rats, Inbred Strains •
             Receptors, Muscarinic • Receptors, Nicotinic •
             Scopolamine • drug effects • pharmacology •
             pharmacology* • physiology • physiology*},
   Abstract = {Pharmacologic studies have indicated that accurate
             performance on the radial-arm maze depends upon the
             integrity of both nicotinic and muscarinic cholinergic
             neurotransmitter systems and that these systems interact in
             a complex fashion. Although numerous studies have suggested
             that pathways deriving from the basal nuclear complex of the
             forebrain are critical for the cholinergic modulation of
             learning and memory, most have focussed on the
             septohippocampal projection, and none have specifically
             targeted the medial or lateral systems. In Experiment 1,
             cortical knife cuts interrupting the medial cholinergic
             pathway were made at the level of the caudate-putamen
             nucleus. Such transections produced a robust but temporary
             disruption of choice accuracy performance in the radial-arm
             maze. Recovery of this behavior occurred within 10 days and
             before cholinergic fiber regeneration, suggesting that
             compensatory changes could have taken place in non-ablated
             neuronal circuits. In Experiment 2, daily postsurgical
             administration of arecoline, an agonist with predominantly
             muscarinic actions, was found to virtually eliminate the
             adverse behavioral effects of medial pathway transections,
             indicating that the deficit could be attributable, in part,
             to disruption of cholinergic projections. In Experiment 3,
             the effects of scopolamine, a muscarinic antagonist, and
             mecamylamine, a nicotinic antagonist, were examined in rats
             with medial cholinergic pathway transections after behavior
             had returned postsurgically to control levels. Although both
             drugs attenuated radial-arm maze performance before knife
             cuts, only scopolamine reduced choice accuracy following
             surgery. We conclude that the medial cholinergic pathway,
             particularly its nicotinic actions, plays an important role
             in cognitive function, at least as exemplified by radial-arm
             maze performance. Muscarinic mechanisms associated with
             other telencephalically projecting cholinergic networks, as
             well as possibly with the medial pathway itself, appear to
             operate interactively with nicotinic influences.},
   Doi = {10.1016/0306-4522(91)90256-n},
   Key = {fds274487}
}

@article{fds274428,
   Author = {Levin, ED and McGurk, SR and Rose, JE and Butcher,
             LL},
   Title = {Cholinergic-dopaminergic interactions in cognitive
             performance.},
   Journal = {Behavioral and Neural Biology},
   Volume = {54},
   Number = {3},
   Pages = {271-299},
   Year = {1990},
   Month = {November},
   ISSN = {0163-1047},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2078161},
   Keywords = {Acetylcholine • Animals • Brain • Cognition
             • Discrimination Learning • Dopamine • Humans
             • Mental Recall • Orientation • Rats •
             Receptors, Cholinergic • Receptors, Dopamine •
             physiology • physiology*},
   Abstract = {Both acetylcholinergic (ACh) and dopaminergic (DA) systems
             have been found to be crucial for the maintenance of
             accurate cognitive performance. In a series of studies
             examining those aspects of cognitive function revealed by
             the radial-arm maze, we have found that these two
             neurotransmitter systems interact in a complex fashion.
             Choice accuracy deficits in the radial-arm maze can be
             induced by blockade of either muscarinic- or nicotinic-ACh
             receptors. The choice accuracy deficit induced by blockade
             of muscarinic receptors with scopolamine can be reversed by
             the DA receptor blocker, haloperidol. The specific DA D1
             blocker SCH 23390 also has this effect, whereas the specific
             D2 blocker raclopride does not, implying that it is D1
             blockade that is critical for reversing the scopolamine
             effect. On the other hand, the choice accuracy deficit
             induced by nicotinic blockade with mecamylamine is
             potentiated by haloperidol. This effect is also seen with
             the D2 antagonist raclopride, but not with the D1 antagonist
             SCH 23390, implying that it is the D2 receptor which is
             important for the potentiation of the mecamylamine effect.
             The relevance of the D2 receptor for nicotinic actions on
             cognitive function is emphasized by the finding that the
             selective D2 agonist LY 171555 reverses the choice accuracy
             deficit caused by mecamylamine. Nicotinic and muscarinic
             blockade are synergistic in the deficit they produce.
             Antagonist doses subthreshold when given alone produce a
             pronounced impairment when given together. This latter
             deficit can be reversed by the D2 agonist LY 171555. These
             studies have outlined the complex nature of ACh-DA
             interactions with regard to cognitive function. Possible
             neural circuits for these interactions are discussed. The
             effectiveness of these selective DA treatments in reversing
             cognitive deficits due to ACh underactivation suggests a
             novel approach to treating cognitive dysfunction in
             syndromes such as Alzheimer's disease.},
   Doi = {10.1016/0163-1047(90)90639-n},
   Key = {fds274428}
}

@article{fds274376,
   Author = {Grijalva, CV and Levin, ED and Morgan, M and Roland, B and Martin,
             FC},
   Title = {Contrasting effects of centromedial and basolateral
             amygdaloid lesions on stress-related responses in the
             rat.},
   Journal = {Physiology & Behavior},
   Volume = {48},
   Number = {4},
   Pages = {495-500},
   Year = {1990},
   Month = {October},
   ISSN = {0031-9384},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2075198},
   Keywords = {Amygdala • Animals • Behavior, Animal •
             Flumazenil • Killer Cells, Natural • Pain
             Measurement • Rats • Rats, Inbred Strains •
             Reaction Time • Spleen • Stereotaxic Techniques
             • Stress, Psychological • anatomy & histology
             • cytology • pharmacology • physiology •
             physiology* • physiopathology*},
   Abstract = {The effects of lesions in the centromedial and basolateral
             amygdala were examined using three different tests sensitive
             to the following stress-related responses: exploratory
             behavior, pain reactivity, and immune responses. The most
             clear-cut results were found with exploratory behavior. Rats
             with lesions of the centromedial amygdala tended to explore
             a radial-arm maze more quickly and entered more novel arms
             of the maze than controls. Those with lesions of the
             basolateral amygdala were generally too hesitant to explore
             at all. No significant differences were found between groups
             on measurements of natural killer cell activity. In tests of
             pain perception, rats in the control group displayed an
             analgesic response on the hot plate following an injection
             of the anxiogenic drug, RO 15-1788, whereas rats with
             centromedial lesions tended to exhibit a blunted response.
             These findings provide modest support for the view that the
             central and lateral regions of the amygdala play
             complementary roles in aversively motivated behaviors and in
             stress-related response patterns.},
   Doi = {10.1016/0031-9384(90)90289-g},
   Key = {fds274376}
}

@article{fds274451,
   Author = {Levin, ED and Behm, F and Rose, JE},
   Title = {The use of flavor in cigarette substitutes.},
   Journal = {Drug and Alcohol Dependence},
   Volume = {26},
   Number = {2},
   Pages = {155-160},
   Year = {1990},
   Month = {October},
   ISSN = {0376-8716},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2242716},
   Keywords = {Adult • Aged • Female • Humans • Male
             • Middle Aged • Motivation • Nicotine •
             Plants, Toxic* • Smoking • Taste* • Tobacco*
             • administration & dosage • prevention & control*
             • psychology},
   Abstract = {Cigarette smokers identify flavor as an important factor in
             the pleasure derived from smoking and for their choice of
             cigarette brand. The issue of cigarette flavor has received
             a great deal of study by cigarette manufacturers but
             relatively little by academic investigators. The paucity of
             literature is particularly acute in terms of the importance
             of flavor in cigarette substitutes, which are used to help
             people to reduce or quit smoking. In the current study, five
             different types of flavors added to a plastic cigarette
             substitute were assessed in experienced smokers. There were
             two menthol-like flavors and three tobacco-like flavors. Two
             groups of smokers were tested: menthol smokers and "regular"
             (non-menthol) smokers. Both types of smokers liked the two
             menthol flavors significantly more than placebo and rated
             the menthol flavors and the cigarette flavor as
             significantly more satisfying than placebo. Craving was
             differentially reduced in the two groups of smokers. Menthol
             smokers showed a small reduction in craving with the
             placebo, with a significant enhancement of this reduction
             seen with the addition of the "EZ Quit" menthol
             flavor.},
   Doi = {10.1016/0376-8716(90)90122-u},
   Key = {fds274451}
}

@article{fds274375,
   Author = {Levin, ED and Rose, JE and Behm, F},
   Title = {Development of a citric acid aerosol as a smoking cessation
             aid.},
   Journal = {Drug and Alcohol Dependence},
   Volume = {25},
   Number = {3},
   Pages = {273-279},
   Year = {1990},
   Month = {June},
   ISSN = {0376-8716},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2189719},
   Keywords = {Aerosols • Analysis of Variance • Citrates •
             Citric Acid • Consumer Satisfaction* • Evaluation
             Studies • Flavoring Agents • Humans •
             Nebulizers and Vaporizers* • Nicotine • Randomized
             Controlled Trials • Respiratory System • Sensation
             • Smoking • Trachea • administration &
             dosage* • drug effects • drug effects* •
             pharmacology • physiology • prevention & control*
             • therapeutic use},
   Abstract = {The satisfaction derived from smoking depends not only on
             the pharmacological effects of nicotine but also the sensory
             stimulation from smoke inhalation, particularly the tracheal
             'scratch'. In a previous study, we found that a citric acid
             aerosol produces a tracheal 'scratch' and provides some of
             the same satisfaction as cigarette smoke. In the present
             study, we evaluated a new pocket-sized device for delivering
             a citric acid aerosol and examined some of the important
             variables for providing a satisfying substitute for
             cigarettes. In the first experiment, volunteers who smoked
             at least 10 cigarettes per day compared a citric acid
             aerosol (either alone or with flavor additives) to a
             cigarette and a placebo. The addition of cigarette smoke
             flavor was found to best enhance the satisfaction provided
             by the citric acid aerosol. In the second experiment,
             smokers were given compact citric acid inhalers to use
             throughout 8 h of cigarette deprivation. The degree of
             satisfaction was highly correlated with the intensity of
             throat sensation provided by the aerosol. This citric acid
             aerosol inhaler may provide a useful tool for smokers while
             trying to quit smoking.},
   Doi = {10.1016/0376-8716(90)90152-5},
   Key = {fds274375}
}

@article{fds274371,
   Author = {Levin, ED and Lee, C and Rose, JE and Reyes, A and Ellison, G and Jarvik,
             M and Gritz, E},
   Title = {Chronic nicotine and withdrawal effects on radial-arm maze
             performance in rats.},
   Journal = {Behavioral and Neural Biology},
   Volume = {53},
   Number = {2},
   Pages = {269-276},
   Year = {1990},
   Month = {March},
   ISSN = {0163-1047},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2331235},
   Keywords = {Animals • Attention • Choice Behavior •
             Discrimination Learning • Drug Implants • Male
             • Mental Recall • Nicotine • Orientation
             • Rats • Rats, Inbred Strains • Substance
             Withdrawal Syndrome • drug effects • drug effects*
             • pharmacology* • psychology*},
   Abstract = {Rats were tested for choice accuracy in an eight-arm radial
             maze during and after chronic administration of nicotine via
             subcutaneously implanted glass and Silastic capsules.
             Nicotine administration significantly improved choice
             accuracy relative to controls. The effect gradually became
             apparent over the first 2 weeks of exposure and persisted
             through the third week. Surprisingly, the significant
             facilitation of the nicotine-treated rats relative to
             controls continued for 2 weeks after the end of nicotine
             administration. No effects of nicotine were seen on choice
             latency or the strategy to make adjacent arm
             entries.},
   Doi = {10.1016/0163-1047(90)90509-5},
   Key = {fds274371}
}

@article{fds274374,
   Author = {Rose, JE and Levin, ED and Behm, FM and Adivi, C and Schur,
             C},
   Title = {Transdermal nicotine facilitates smoking
             cessation.},
   Journal = {Clinical Pharmacology and Therapeutics},
   Volume = {47},
   Number = {3},
   Pages = {323-330},
   Year = {1990},
   Month = {March},
   ISSN = {0009-9236},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2178852},
   Keywords = {Administration, Cutaneous • Double-Blind Method •
             Female • Humans • Male • Nicotine •
             Randomized Controlled Trials • Smoking • Tobacco
             Use Disorder • administration & dosage* • adverse
             effects • prevention & control* •
             psychology*},
   Abstract = {The efficacy of a transdermal nicotine patch in facilitation
             of smoking cessation was evaluated in a randomized
             double-blind trial. Sixty-five smokers who were highly
             dependent on cigarettes participated in the study, which
             included a behavioral smoking-cessation program. The rates
             of continuous abstinence were significantly higher in the
             nicotine group both initially (55% versus 34%) and at 3
             weeks (18% versus 6%). Certain smoking withdrawal symptoms,
             including negative affect and hypoarousal, were effectively
             relieved by the nicotine patch. There was a trend toward a
             reduction in cigarette craving, whereas hunger and habit
             withdrawal symptoms were not affected. The main side effect
             associated with the nicotine patch was skin irritation.
             These findings suggest that a nicotine skin patch may be a
             useful aid to smoking cessation; however, the combination of
             other techniques with nicotine replacement may provide a
             more effective treatment for symptoms such as craving for
             cigarettes.},
   Doi = {10.1038/clpt.1990.35},
   Key = {fds274374}
}

@article{fds274403,
   Author = {Levin, ED and Rose, JE and McGurk, SR and Butcher,
             LL},
   Title = {Characterization of the cognitive effects of combined
             muscarinic and nicotinic blockade.},
   Journal = {Behavioral and Neural Biology},
   Volume = {53},
   Number = {1},
   Pages = {103-112},
   Year = {1990},
   Month = {January},
   ISSN = {0163-1047},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/1967931},
   Keywords = {(R)-2,3,4,5-Tetrahydro-8-chloro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol
             • Animals • Appetitive Behavior •
             Benzazepines • Brain • Discrimination Learning
             • Dopamine Agents • Dopamine Antagonists •
             Ergolines • Female • Mecamylamine • Memory
             • Mental Recall • Orientation • Quinpirole
             • Rats • Reaction Time • Receptors,
             Muscarinic • Receptors, Nicotinic • Scopolamine
             • drug effects • drug effects* • pharmacology
             • pharmacology*},
   Abstract = {Choice accuracy performance in the radial-arm maze is
             dependent upon the integrity of both the nicotinic and
             muscarinic cholinergic receptors. Pharmacological blockade
             of either of these subtypes of cholinergic receptors with
             mecamylamine or scopolamine impairs choice accuracy in the
             radial-arm maze. We have previously demonstrated that the
             performance deficit caused by muscarinic blockade is
             exacerbated in at least an additive fashion by
             coadministration of the nicotinic antagonist, mecamylamine.
             In the present study, it was found that mecamylamine and
             scopolamine act together in a greater than additive fashion
             in disrupting radial-arm maze choice accuracy. When doses of
             these drugs which do not by themselves cause significant
             impairments in choice accuracy are given together, they
             induce a pronounced impairment. Previous results have shown
             that the adverse effects of nicotinic blockade could be
             reversed by the dopaminergic D2 agonist LY 171555. In this
             study, this drug was found to attenuate the cognitive
             impairment caused by combined nicotinic and muscarinic
             blockade. On the other hand, the dopaminergic D1 antagonist
             SCH 23390 which has previously been shown to reverse the
             adverse effects of muscarinic blockade was not found in this
             study to attenuate the impairment of combined nicotinic and
             muscarinic blockade. Since combined nicotinic and muscarinic
             blockade approximates generalized cholinergic
             underactivation, treatments like LY 171555, which attenuate
             the adverse effects of this combined blockade, may be useful
             in treating syndromes like Alzheimer's disease, which are
             characterized by generalized cholinergic
             loss.},
   Doi = {10.1016/0163-1047(90)90865-4},
   Key = {fds274403}
}

@article{fds274444,
   Author = {Levin, ED and DeLuna, R and Uemura, E and Bowman,
             RE},
   Title = {Long-term effects of developmental halothane exposure on
             radial arm maze performance in rats.},
   Journal = {Behavioural Brain Research},
   Volume = {36},
   Number = {1-2},
   Pages = {147-154},
   Year = {1990},
   Month = {January},
   ISSN = {0166-4328},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2302314},
   Keywords = {Age Factors • Animals • Discrimination Learning
             • Dose-Response Relationship, Drug • Female •
             Halothane • Male • Memory • Mental Recall
             • Orientation • Pregnancy • Prenatal Exposure
             Delayed Effects* • Rats • Reaction Time •
             Retention (Psychology) • drug effects • drug
             effects* • pharmacology*},
   Abstract = {Chronic exposure of rats to low levels of halothane during
             development, a treatment which retards synaptogenesis, was
             found to cause a long-term impairment of choice accuracy in
             the radial-arm maze. In Expt. 1, the relative importance of
             dose level and dosing regimen was examined. Dose level
             seemed the more critical variable for causing impaired
             choice accuracy. Exposure to 100 parts per million (ppm) of
             halothane in the air either on an intermittent or continuous
             schedule from day two of conception until 60 days after
             birth significantly impaired choice accuracy, whereas
             exposure to 25 ppm on a continuous schedule did not cause a
             deficit, even though with this condition the total amount of
             halothane exposure was about the same as with 100 ppm given
             intermittently. In Expt. 2, the 100 ppm intermittent
             exposure regimen was used to examine the relative importance
             of exposure during early and late developmental periods for
             producing the cognitive effects of halothane. Groups were
             divided into those exposed to halothane during gestation and
             until 30 days after birth (early exposure), those exposed
             from day 31 until day 90 (late exposure) and those exposed
             during both early and late periods (combined exposure).
             Adverse effects on choice accuracy were seen with all 3
             types of exposure, but surprisingly, it was the late
             exposure that caused the most severe effects. These results
             show that developmental exposure to halothane which impairs
             synaptogenesis also causes long-lasting cognitive
             impairment. Halothane exposure can be a useful experimental
             tool for examining the relationship between synaptic and
             behavioral development.},
   Doi = {10.1016/0166-4328(90)90168-e},
   Key = {fds274444}
}

@article{fds274354,
   Author = {Levin, ED and Rose, JE},
   Title = {Anticholinergic sensitivity following chronic nicotine
             administration as measured by radial-arm maze performance in
             rats.},
   Journal = {Behav Pharmacol},
   Volume = {1},
   Number = {6},
   Pages = {511-520},
   Year = {1990},
   ISSN = {0955-8810},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/11175437},
   Abstract = {Chronic nicotine administration in rats has been previously
             found to improve choice accuracy performance of rats in the
             radial-arm maze. A nicotine-induced choice accuracy
             improvement was also seen in the current study. Rats were
             trained to asymptotic levels of choice accuracy performance
             on a working memory paradigm in an 8-arm radial maze. During
             and after 3 weeks of chronic nicotine treatment, rats were
             tested for sensitivity to acute doses of the nicotinic and
             muscarinic receptor antagonists, mecamylamine and
             scopolamine. During the first week of administration,
             nicotine-treated rats were supersensitive to the sedation
             caused by mecamylamine. This suggests that nicotine may not
             have been acting as a simple nicotinic agonist, since in
             this case, the opposite effect, an attenuated effect of
             mecamylamine in the nicotine-treated group, would have been
             expected. Three to 4 weeks after withdrawal from chronic
             nicotine administration, the treated rats were more
             sensitive to the choice accuracy deficits caused by the
             muscarinic blocker scopolamine (0.16 mg/kg) and the
             nicotinic blocker mecamylamine (10 mg/kg). This
             supersensitivity may have been due to a lasting change
             caused by chronic nicotine in the cholinergic bases of
             memory function.},
   Key = {fds274354}
}

@article{fds274412,
   Author = {Levin, ED and Bushnell, PJ and Baysinger, CM},
   Title = {d-Amphetamine-induced "floating limb" syndrome in young
             rhesus monkeys.},
   Journal = {Psychopharmacology},
   Volume = {101},
   Number = {1},
   Pages = {112-117},
   Year = {1990},
   ISSN = {0033-3158},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2343071},
   Keywords = {Animals • Athetosis • Behavior, Animal •
             Dextroamphetamine • Macaca mulatta • Motor
             Activity • Tremor • chemically induced •
             chemically induced* • drug effects • drug effects*
             • pharmacology*},
   Abstract = {Acute d-amphetamine administration to young rhesus monkeys
             (N = 10) caused a motor syndrome of hypoactivity and
             chorea-like postures and motor movements which we have
             termed "floating limb". Frequently after subcutaneous
             injections of 0.3 or 0.6 mg/kg d-amphetamine, an affected
             monkey raised one or both legs or arms and held the limb(s)
             motionless in the air. Affected limbs were usually returned
             to a normal position if they appeared to enter the animal's
             visual field. In other cases, the monkey assumed bizarre and
             contorted postures which were held for prolonged periods.
             Such postures were often accompanied by gentle repetitive
             brushing of the ears and facial hair with extremities of the
             affected limbs. Quantification of the frequency of these
             movements showed that they occurred regularly for 90-150 min
             after d-amphetamine. Hydroxyamphetamine, a
             peripherally-acting amphetamine analog, did not induce
             floating limb, indicating that the behavior was probably
             mediated by central actions of d-amphetamine. A similar
             disorder has been reported occasionally in other studies
             with monkeys and cats. It may be related to the chorea that
             is seen in humans after the use of amphetamine and other
             stimulants. d-Amphetamine treatment in young monkeys may
             provide a viable model of human choreoathetoid disorders
             induced by disease or drug use.},
   Doi = {10.1007/bf02253727},
   Key = {fds274412}
}

@article{fds274416,
   Author = {Behm, FM and Levin, ED and Lee, YK and Rose, JE},
   Title = {Low-nicotine regenerated smoke aerosol reduces desire for
             cigarettes.},
   Journal = {Journal of Substance Abuse},
   Volume = {2},
   Number = {2},
   Pages = {237-247},
   Year = {1990},
   ISSN = {0899-3289},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2136112},
   Keywords = {Adult • Aerosols • Dose-Response Relationship,
             Drug • Female • Humans • Male • Middle
             Aged • Nebulizers and Vaporizers • Nicotine •
             Particle Size • Smoke* • Smoking Cessation •
             administration & dosage* • methods*},
   Abstract = {We have developed a method of producing an aerosol with many
             of the sensory qualities of cigarette smoke, but with only
             3% of the tar and nicotine and none of the carbon monoxide
             of a typical commercial cigarette. The aerosol was generated
             from a suspension of 1% cigarette smoke condensate in 10%
             ethanol. The aerosol, generated with an ultrasonic
             nebulizer, resembled smoke visually but had a larger
             particle size than cigarette smoke (3.5 microns vs. 0.5
             micron mass median diameter). Twelve smokers rated blocks of
             10 puffs of aerosolized smoke solution, a popular commercial
             cigarette, and an unlit cigarette (control). The blocks of
             puffs were evaluated for sensory qualities and smoking
             satisfaction obtained. The rated strength of the smoke
             aerosol was comparable to that of the commercial cigarette.
             The aerosol was rated significantly more desirable and more
             satisfying than the control, though not as desirable as the
             commercial cigarette. Surprisingly, the smoke aerosol
             reduced self-reported desire for cigarettes as much as the
             commercial cigarette. This new method is a promising
             approach for evaluating the role of sensory cues in smoking,
             and it may also be useful as a clinical tool for smoking
             cessation.},
   Doi = {10.1016/s0899-3289(05)80058-6},
   Key = {fds274416}
}

@article{fds274479,
   Author = {Uemura, E and Levin, ED and DeLuna, R and Bowman,
             RE},
   Title = {Suppressive effects of halothane on reactive synaptogenesis
             in the dentate gyrus of rats.},
   Journal = {Brain Research},
   Volume = {496},
   Number = {1-2},
   Pages = {317-320},
   Year = {1989},
   Month = {September},
   ISSN = {0006-8993},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2804641},
   Keywords = {Animals • Axons • Halothane • Hippocampus
             • Male • Nerve Regeneration • Rats •
             Rats, Inbred Strains • Synapses • Time Factors
             • drug effects • drug effects* •
             pharmacology* • physiology* • ultrastructure},
   Abstract = {Reactive synaptogenesis was studied in the dentate gyrus of
             rats exposed to 100 parts per million of halothane for 15
             days starting on the day after unilateral entorhinal
             lesioning. Halothane exposure markedly affected the
             replacement of synapses. Only 17% of the lost synapses were
             restored by day 15 postlesion in rats exposed to halothane,
             while 73% of the lost synapses were recovered in rats not
             exposed to halothane. However, this suppression in initial
             reactive synaptogenesis did not result in permanent deficits
             in synaptic population. After halothane exposure was
             stopped, reactive synaptogenesis resumed, and by day 30
             after the lesion, the synaptic population of the
             experimental group caught up to the control level. This
             suppressive action of halothane suggests its utility as a
             research tool for delaying synaptogenesis during selected
             developmental epochs to study the relationship between
             synaptic and behavioral recovery.},
   Doi = {10.1016/0006-8993(89)91080-9},
   Key = {fds274479}
}

@article{fds274453,
   Author = {Levin, ED and See, RE and South, D},
   Title = {Effects of dopamine D1 and D2 receptor antagonists on oral
             activity in rats.},
   Journal = {Pharmacology, Biochemistry, and Behavior},
   Volume = {34},
   Number = {1},
   Pages = {43-48},
   Year = {1989},
   Month = {September},
   ISSN = {0091-3057},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2576312},
   Keywords = {(R)-2,3,4,5-Tetrahydro-8-chloro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol
             • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
             • Animals • Benzazepines • Data Collection
             • Dopamine Agents • Dopamine Antagonists* •
             Dose-Response Relationship, Drug • Drug Interactions
             • Ergolines • Female • Head •
             Mastication • Motor Activity • Quinpirole •
             Rats • Rats, Inbred Strains • Sulpiride •
             drug effects* • methods • pharmacology •
             pharmacology*},
   Abstract = {Two experiments were performed to investigate the actions of
             the selective D1 blocker SCH 23390 and the selective D2
             blocker sulpiride, on oral movements in rats; these were
             quantified by a human observer scoring vacuous chewing
             movements (VCMs), jaw tremor and head movements, as well as
             a computer analysis system which measured the amplitude and
             slope of each movement. In the first experiment it was found
             that both SCH 23390 and sulpiride decreased VCMs and head
             movements in a dose-dependent manner, with SCH 23390 more
             effectively decreasing head movements and sulpiride more
             effectively decreasing VCMs. In a second experiment, the
             effectiveness of these two drugs in blocking the actions of
             selective D1 (SKF 38393) and D2 (LY 171555) agonists was
             studied. The SKF 38393-induced increase in computer-scored
             movement was attenuated by both sulpiride and SCH 23390,
             whereas the LY 171555-induced decrease in VCMs was
             attenuated by sulpiride, while SCH 23390 exacerbated it.
             These findings, together with our earlier results, suggest a
             simple relationship of D1 receptors to oral movement, with
             increased activation resulting in increased oral movement
             and decreased activation resulting in decreased oral
             movement. The relationship of D2 receptors to oral movement
             shows a more complex pattern, with both stimulation and
             blockade decreasing oral movement. One possibility may be
             the existence of more than one subpopulation of D2 receptors
             mediating these effects.},
   Doi = {10.1016/0091-3057(89)90350-x},
   Key = {fds274453}
}

@article{fds274489,
   Author = {Levin, ED and McGurk, SR and Rose, JE and Butcher,
             LL},
   Title = {Reversal of a mecamylamine-induced cognitive deficit with
             the D2 agonist, LY 171555.},
   Journal = {Pharmacology, Biochemistry, and Behavior},
   Volume = {33},
   Number = {4},
   Pages = {919-922},
   Year = {1989},
   Month = {August},
   ISSN = {0091-3057},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2575760},
   Keywords = {2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
             • Animals • Choice Behavior • Dopamine Agents
             • Drug Interactions • Ergolines • Female
             • Mecamylamine • Quinpirole • Rats •
             Rats, Inbred Strains • Receptors, Dopamine •
             classification • drug effects • drug effects*
             • pharmacology* • physiology*},
   Abstract = {Pharmacological blockade of either nicotinic or muscarinic
             cholinergic receptors has been found to impair choice
             accuracy in the radial-arm maze. Simultaneous blockade of
             both of these receptor types causes an additive impairment.
             However, despite these common effects, nicotinic and
             muscarinic receptors have been found to have differential
             involvement with dopamine receptors. The cognitive
             impairment caused by the muscarinic antagonist scopolamine
             is reversed by the D1 antagonist SCH 23390 but is unaffected
             by the D2 antagonist raclopride. In contrast, the cognitive
             impairment caused by the nicotinic antagonist mecamylamine
             is unaffected by SCH 23390 but is potentiated by raclopride.
             In the current study, the D2 agonist LY 171555 was found to
             be effective in reversing the radial-arm maze choice
             accuracy impairment caused by mecamylamine. In contrast, the
             D1 agonist SKF 38393 was not found to be effective. Thus, we
             have found selective dopaminergic D1 and D2 treatments which
             counteract the adverse cognitive effects of either nicotinic
             or muscarinic blockade. A combination of these treatments
             may be useful in treating the cognitive effects of
             generalized cholinergic underactivation.},
   Doi = {10.1016/0091-3057(89)90494-2},
   Key = {fds274489}
}

@article{fds274407,
   Author = {Levin, ED and Ellison, GD and See, RE and South, D and Young,
             E},
   Title = {D1 and D2 dopamine receptor interactions with
             pilocarpine-induced oral activity in rats.},
   Journal = {Pharmacology, Biochemistry, and Behavior},
   Volume = {33},
   Number = {3},
   Pages = {501-505},
   Year = {1989},
   Month = {July},
   ISSN = {0091-3057},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2573903},
   Keywords = {(R)-2,3,4,5-Tetrahydro-8-chloro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol
             • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
             • Animals • Benzazepines • Dopamine Agents
             • Dopamine Antagonists* • Dose-Response
             Relationship, Drug • Drug Interactions • Ergolines
             • Female • Mouth • Movement •
             Pilocarpine • Quinpirole • Rats • Rats,
             Inbred Strains • Receptors, Dopamine • Receptors,
             Dopamine D1 • Receptors, Dopamine D2 • drug
             effects • drug effects* • pharmacology •
             pharmacology* • physiology},
   Abstract = {To investigate the relationship between dopamine (DA) and
             acetylcholine (ACh) systems in the control of oral movement,
             we studied the effects of specific D1 and D2 drugs on
             vacuous chewing movements induced by the muscarinic ACh
             agonist, pilocarpine. In previous experiments we found that
             when given alone, the D1 agonist SKF 38393 increased vacuous
             chewing and the D1 antagonist SCH 23390 decreased it, while
             both the D2 agonist LY 171555 (quinpirole) and the D2
             antagonist sulpiride decreased vacuous chewing. In the
             present experiment, the effects of the D1 drugs had similar
             effects in rats concurrently given pilocarpine. In contrast,
             the effects of both of the D2 drugs were altered by
             pilocarpine. Surprisingly, the actions of D2 agonist and
             antagonist were affected in opposite ways. The effect of
             sulpiride in reducing oral movement activity was eliminated
             by pilocarpine, while the effect of LY 171555 in reducing
             oral movement was enhanced by pilocarpine.},
   Doi = {10.1016/0091-3057(89)90376-6},
   Key = {fds274407}
}

@article{fds274445,
   Author = {McGurk, SR and Levin, ED and Butcher, LL},
   Title = {Nicotinic-dopaminergic relationships and radial-arm maze
             performance in rats.},
   Journal = {Behavioral and Neural Biology},
   Volume = {52},
   Number = {1},
   Pages = {78-86},
   Year = {1989},
   Month = {July},
   ISSN = {0163-1047},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2757586},
   Keywords = {Animals • Behavior, Animal • Dose-Response
             Relationship, Drug • Drug Synergism • Female
             • Haloperidol • Learning • Mecamylamine
             • Memory • Rats • Rats, Inbred Strains •
             Reaction Time • Receptors, Dopamine • Receptors,
             Muscarinic • Receptors, Nicotinic • Scopolamine
             • drug effects • drug effects* •
             pharmacology* • physiology},
   Abstract = {Accurate performance on the radial-arm maze is dependent
             upon the integrity of nicotinic-cholinergic,
             muscarinic-cholinergic, and dopaminergic systems.
             Pharmacological blockade of these systems with mecamylamine,
             scopolamine, or haloperidol impairs choice accuracy in the
             maze. We have previously demonstrated that the performance
             deficit caused by muscarinic blockade is enhanced by
             coadministration of the nicotinic antagonist, mecamylamine,
             and is diminished by coadministration of the dopamine
             antagonist, haloperidol. In the present study, it was found
             that the choice accuracy deficit produced by nicotinic
             blockade is enhanced, not antagonized, by coadministration
             of haloperidol. Thus, although both nicotinic and muscarinic
             cholinergic systems are involved in radial-arm maze
             performance and antagonists of these receptors are additive
             in the deficits they cause, nicotinic and muscarinic
             interactions with dopaminergic systems are opposite in
             nature.},
   Doi = {10.1016/s0163-1047(89)90182-9},
   Key = {fds274445}
}

@article{fds274331,
   Author = {Levin, ED and Rose, JE and Behm, F},
   Title = {Controlling puff volume without disrupting smoking
             topography},
   Journal = {Behavior Research Methods, Instruments, &
             Computers},
   Volume = {21},
   Number = {3},
   Pages = {383-386},
   Publisher = {Springer Nature},
   Year = {1989},
   Month = {May},
   ISSN = {0743-3808},
   url = {http://dx.doi.org/10.3758/BF03202801},
   Abstract = {In studies of the behavioral and physiological effects of
             cigarette smoking, it is of critical importance to keep the
             dose of nicotine as constant as possible. This is difficult
             with smoking, because when the nicotine delivery of a
             cigarette is increased or reduced, smokers tend to
             compensate by modifying their smoke intake. In a laboratory
             study, it is relatively easy to control the number of
             cigarettes and the number of puffs taken, but it is more
             difficult to control the volume of each puff. Various
             procedures have been developed to control puff volume, but
             they have a disadvantage of disrupting the normal topography
             of smoking. We have developed an apparatus for delivering
             fixed volumes of smoke that has given consistent tar and
             nicotine values needed in studies of the behavioral and
             physiological effects of cigarette smoking. This method has
             the distinct advantage of allowing the subject to inhale the
             smoke in a normal fashion, with a draw resistance comparable
             to that of a cigarette. The device is inexpensive and easy
             to make. © 1989 Psychonomic Society, Inc.},
   Doi = {10.3758/BF03202801},
   Key = {fds274331}
}

@article{fds274476,
   Author = {Schantz, SL and Levin, ED and Bowman, RE and Heironimus, MP and Laughlin, NK},
   Title = {Effects of perinatal PCB exposure on discrimination-reversal
             learning in monkeys.},
   Journal = {Neurotoxicology and Teratology},
   Volume = {11},
   Number = {3},
   Pages = {243-250},
   Year = {1989},
   Month = {May},
   ISSN = {0892-0362},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2502707},
   Keywords = {Adipose Tissue • Animals • Animals, Suckling*
             • Aroclors • Discrimination Learning • Female
             • Macaca mulatta • Maternal-Fetal Exchange* •
             Milk, Human • Polychlorinated Biphenyls •
             Pregnancy • Reversal Learning • analysis •
             drug effects* • toxicity*},
   Abstract = {Monkeys exposed to PCB mixtures during gestation and
             lactation were tested on two-choice discrimination-reversal
             learning (DR). In Experiment 1, offspring of mothers fed 1.0
             ppm Aroclor 1248, and offspring born 1.5 years after
             maternal exposure to 2.5 ppm Aroclor 1248 ended did not
             differ from controls on spatial, color or shape DR problems.
             In Experiment 2, offspring of mothers fed 0.25 or 1.0 ppm
             Aroclor 1016 and offspring born 3 years after maternal
             exposure to 2.5 ppm Aroclor 1248 ended were tested on the
             same spatial, color and shape problems, but a spatial
             problem with color and shape as irrelevant cues was inserted
             after the initial spatial problem. Performance of the high
             dose Aroclor 1016 offspring was impaired on the initial
             spatial problem, and facilitated on the shape problem.
             Performance of the Aroclor 1248 postexposure offspring was
             facilitated on the shape problem. This apparently
             facilitatory effect may represent a failure of PCB-exposed
             monkeys to learn the irrelevancy of the shape cue when it
             was initially presented.},
   Doi = {10.1016/0892-0362(89)90066-4},
   Key = {fds274476}
}

@article{fds274379,
   Author = {Rose, JE and Sampson, A and Levin, ED and Henningfield,
             JE},
   Title = {Mecamylamine increases nicotine preference and attenuates
             nicotine discrimination.},
   Journal = {Pharmacology, Biochemistry, and Behavior},
   Volume = {32},
   Number = {4},
   Pages = {933-938},
   Year = {1989},
   Month = {April},
   ISSN = {0091-3057},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2798542},
   Keywords = {Adult • Discrimination (Psychology) •
             Dose-Response Relationship, Drug • Drive • Humans
             • Male • Mecamylamine • Middle Aged •
             Nicotine • Personal Satisfaction • Self
             Administration • Smoking • administration & dosage
             • drug effects* • pharmacology* •
             physiopathology • psychology*},
   Abstract = {Eight subjects evaluated various qualities of cigarette
             smoke after being given a range of doses (0, 2.5, 10 and 20
             mg) of the nicotinic receptor blocker mecamylamine. In one
             test condition, subjects were given either high or low
             nicotine tobacco smoke to determine the effects of
             mecamylamine on their subjective responses. In another test
             condition, subjects were allowed to adjust the nicotine dose
             level of the smoke to determine the effects of mecamylamine
             on dose preference. When the subjects evaluated puffs of
             smoke with high and low nicotine content, mecamylamine
             caused a dose-related decrease in the self-rated strength
             and harshness of the high nicotine dose level smoke. In
             contrast, there was little effect on the low dose smoke. At
             the highest mecamylamine dose (20 mg) there was no
             significant difference in the ratings of high and low
             nicotine cigarettes. Low doses of mecamylamine decreased the
             reported desire for a cigarette, and also attenuated the
             reduction in desire for a cigarette caused by smoking. When
             the subjects were allowed to select their preferred level of
             nicotine intake using a smoke mixing device, the 10 and 20
             mg doses of mecamylamine caused a significant increase in
             self-administered nicotine dose level. Despite this
             compensatory increase in nicotine self-administration, the
             reduction in desire for a cigarette after smoking was still
             less than after placebo.},
   Doi = {10.1016/0091-3057(89)90061-0},
   Key = {fds274379}
}

@article{fds274392,
   Author = {Levin, ED and McGurk, SR and South, D and Butcher,
             LL},
   Title = {Effects of combined muscarinic and nicotinic blockade on
             choice accuracy in the radial-arm maze.},
   Journal = {Behavioral and Neural Biology},
   Volume = {51},
   Number = {2},
   Pages = {270-277},
   Year = {1989},
   Month = {March},
   ISSN = {0163-1047},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2930437},
   Keywords = {Animals • Brain • Discrimination Learning •
             Female • Mecamylamine • Neurons • Orientation
             • Rats • Rats, Inbred Strains • Reaction Time
             • Receptors, Cholinergic • Receptors, Muscarinic
             • Receptors, Nicotinic • Scopolamine • drug
             effects • drug effects* • pharmacology*},
   Abstract = {Acetylcholine (ACh) systems have been found to be crucial
             for the maintenance of accurate cognitive performance. A
             great variety of studies have shown that the muscarinic ACh
             receptor blocker scopolamine impairs choice accuracy in the
             radial-arm maze. Recently, it has been found that the
             nicotinic ACh receptor blocker mecamylamine also impairs
             radial-arm maze choice accuracy. In the present study, we
             investigated the effects of combined administration of these
             two ACh blockers. Scopolamine (0.15 mg/kg) and mecamylamine
             (10 mg/kg) each moderately impaired choice accuracy.
             Combined treatment with scopolamine and mecamylamine
             significantly decreased choice accuracy relative to either
             drug alone. This combination treatment lowered choice
             accuracy to chance levels. These data show that nicotinic
             and muscarinic blockade have at least additive effects in
             producing an anterograde memory deficit. Concurrent blockade
             of these two components of ACh systems may provide a better
             animal model of cognitive impairments due to the loss of
             cholinergic neurons, such as Alzheimer's
             disease.},
   Doi = {10.1016/s0163-1047(89)90917-5},
   Key = {fds274392}
}

@article{fds322763,
   Author = {Yirmiya, R and Levin, ED and Chapman, CD and Garcia,
             J},
   Title = {Morphological and behavioral effects of perinatal exposure
             to aspartame (Nutrasweet®) on rat pups},
   Journal = {Bulletin of the Psychonomic Society},
   Volume = {27},
   Number = {2},
   Pages = {153-156},
   Publisher = {Springer Nature},
   Year = {1989},
   Month = {January},
   url = {http://dx.doi.org/10.3758/BF03329926},
   Abstract = {Possible side effects of perinatal exposure to
             L-aspartyl-L-phenylalanine methyl ester (aspartame) were
             studied by providing aspartame-containing water to female
             rats from 30 days before conception until the pups were 30
             days of age. Compared with rat pups of mothers who drank
             plain water, aspartame-exposed pups were not different in
             morphological (i.e., pinnae detachment, eye opening, incisor
             eruption, and body weight) and reflex (i.e., surface
             righting and negative geotaxis) development. Additionally,
             no difference was found in the time taken by mothers to
             retrieve their litters. At 30 days of age, performance in a
             radial-arm maze of aspartame-exposed rats differed from that
             of rats not exposed to aspartame. Entries prior to
             repeat-that is, the number of arms chosen until an arm was
             reentered-was higher for the aspartame-exposed rats. Maze
             performance of rats exposed to aspartame for 30 days as
             adults did not differ from that of rats exposed only to
             water. These results suggest that aspartame may either
             facilitate the development of components involved in this
             procedure or reduce factors that interfere with this task.
             © 1989, The Psychonomic Society, Inc.. All rights
             reserved.},
   Doi = {10.3758/BF03329926},
   Key = {fds322763}
}

@article{fds274384,
   Author = {McGurk, SR and Levin, ED and Butcher, LL},
   Title = {Radial-arm maze performance in rats is impaired by a
             combination of nicotinic-cholinergic and D2 dopaminergic
             antagonist drugs.},
   Journal = {Psychopharmacology},
   Volume = {99},
   Number = {3},
   Pages = {371-373},
   Year = {1989},
   ISSN = {0033-3158},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2687921},
   Keywords = {(R)-2,3,4,5-Tetrahydro-8-chloro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol
             • Animals • Benzazepines • Dopamine
             Antagonists* • Drug Interactions • Female •
             Ganglionic Stimulants • Haloperidol • Mecamylamine
             • Parasympathomimetics • Psychomotor Performance
             • Raclopride • Rats • Rats, Inbred Strains
             • Salicylamides • Scopolamine • drug effects*
             • pharmacology • pharmacology*},
   Abstract = {Performance on the radial-arm maze depends on the integrity
             of both cholinergic and dopaminergic systems. We have
             previously found that administration of either the
             nicotinic-cholinergic antagonist, mecamylamine, or the
             muscarinic-cholinergic antagonist, scopolamine, impairs
             choice accuracy in the radial-arm maze. Co-administration of
             the dopaminergic antagonist, haloperidol, ameliorated the
             performance deficit caused by scopolamine but exacerbated
             the deficit caused by mecamylamine. Furthermore, antagonism
             of the effect of scopolamine is due specifically to blockade
             of D1 receptors. In the present experiment behaviorally
             subthreshold doses of mecamylamine and the D2 antagonist
             raclopride impaired maze performance when administered
             together. No interactive effects were observed between
             mecamylamine and the D1 antagonist SCH 23390. Although
             several of the drug treatments studied significantly
             increased choice latency, an index of motor behavior, there
             was no perfect relationship between choice accuracy and
             choice latency. These data indicate that
             nicotinic-cholinergic and muscarinic-cholinergic systems
             interact selectively and differentially with D1 and D2
             dopaminergic systems.},
   Doi = {10.1007/bf00445560},
   Key = {fds274384}
}

@article{fds274493,
   Author = {Levin, ED and Gunne, LM},
   Title = {Chronic neuroleptic effects on spatial reversal learning in
             monkeys.},
   Journal = {Psychopharmacology},
   Volume = {97},
   Number = {4},
   Pages = {496-500},
   Year = {1989},
   ISSN = {0033-3158},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2567030},
   Keywords = {Animals • Antipsychotic Agents • Cebus •
             Female • Male • Reversal Learning • Space
             Perception • drug effects • drug effects* •
             pharmacology*},
   Abstract = {Cebus apella monkeys were chronically administered the
             antipsychotic drug fluphenazine decanoate for periods
             ranging from 3.5 to 5.5 years. In the present study, four of
             these monkeys and two controls were tested for cognitive
             abilities on a spatial learning task, which consisted of an
             original discrimination and four reversals of that
             discrimination. No effect of fluphenazine administration was
             seen in the rate of learning the original discrimination,
             but the carryover of learning across discrimination
             reversals was significantly reduced by fluphenazine. After
             overtraining on the original discrimination, the controls
             showed the normal difficulty in learning the first reversal.
             The fluphenazine-treated monkeys showed no such disruption.
             On subsequent reversals, the controls showed continually
             improving performance, so that on the third and fourth
             reversals they had near-perfect scores. On the other hand,
             the fluphenazine-treated monkeys showed no change over the
             four reversals. Unlike normal monkeys, their learning did
             not improve with practice. Although simple forms of learning
             seem to be relatively unaffected by chronic fluphenazine
             administration, more complex learning is
             disrupted.},
   Doi = {10.1007/bf00439554},
   Key = {fds274493}
}

@article{fds274513,
   Author = {Andersson, U and Häggström, JE and Levin, ED and Bondesson, U and Valverius, M and Gunne, LM},
   Title = {Reduced glutamate decarboxylase activity in the subthalamic
             nucleus in patients with tardive dyskinesia.},
   Journal = {Movement Disorders : Official Journal of the Movement
             Disorder Society},
   Volume = {4},
   Number = {1},
   Pages = {37-46},
   Year = {1989},
   ISSN = {0885-3185},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2927401},
   Keywords = {Aged • Aged, 80 and over • Death, Sudden •
             Dyskinesia, Drug-Induced • Female • Glutamate
             Decarboxylase • Humans • Male • Middle Aged
             • Myocardial Infarction • Thalamic Nuclei •
             deficiency* • pathology • pathology*},
   Abstract = {Glutamate decarboxylase (GAD) activity was measured in the
             nuclei of the basal ganglia in patients with
             neuroleptic-induced tardive dyskinesia (TD) and controls
             matched for age and premortem state. In five TD patients,
             who all had a sudden death, a significant decrease in GAD
             activity was found in the subthalamic nucleus (STN). The
             lowered GAD activity in the STN may represent a biochemical
             substrate for neuroleptic-induced TD.},
   Doi = {10.1002/mds.870040107},
   Key = {fds274513}
}

@article{fds274420,
   Author = {Levin, ED and Bowman, RE},
   Title = {Long-term effects of chronic postnatal lead exposure on
             delayed spatial alternation in monkeys.},
   Journal = {Neurotoxicology and Teratology},
   Volume = {10},
   Number = {6},
   Pages = {505-510},
   Year = {1988},
   Month = {November},
   ISSN = {0892-0362},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/3244342},
   Keywords = {Animals • Conditioning, Operant • Food Preferences
             • Lead Poisoning • Learning* • Macaca mulatta
             • Reference Values • Reward •
             psychology*},
   Abstract = {Two cohorts of monkeys chronically exposed to lead during
             the first year after birth and their controls were tested
             during adulthood for choice accuracy on a learning and
             memory task, delayed spatial alternation (DSA). Neither
             cohort showed significant lead-related deficits, as had been
             seen in a previous experiment with monkeys exposed to
             similar chronic levels of lead during the first year with an
             additional high pulse given five-six weeks after birth
             (18,19). On the contrary, the lead-exposed monkeys in the
             present experiment actually performed slightly better than
             controls. In the previous (pulse-chronic) study, the deficit
             occurred at short intertrial delays, suggesting an
             attentional rather than mnenomic deficit. A lead-induced
             decrease in attentiveness could also explain the present
             results. The lower level lead intoxication may have
             decreased attentiveness to a lesser degree, so that the
             monkeys were less susceptible to irrelevant stimuli and
             performed better.},
   Doi = {10.1016/0892-0362(88)90085-2},
   Key = {fds274420}
}

@article{fds274459,
   Author = {Levin, ED},
   Title = {Scopolamine interactions with D1 and D2 antagonists on
             radial-arm maze performance in rats.},
   Journal = {Behavioral and Neural Biology},
   Volume = {50},
   Number = {2},
   Pages = {240-245},
   Year = {1988},
   Month = {September},
   ISSN = {0163-1047},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2906537},
   Keywords = {(R)-2,3,4,5-Tetrahydro-8-chloro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol
             • Animals • Antipsychotic Agents •
             Benzazepines • Brain • Choice Behavior •
             Discrimination Learning • Female • Orientation
             • Raclopride • Rats • Rats, Inbred Strains
             • Reaction Time • Receptors, Dopamine •
             Receptors, Dopamine D1 • Receptors, Dopamine D2 •
             Receptors, Muscarinic • Salicylamides •
             Scopolamine • drug effects • drug effects* •
             pharmacology • pharmacology*},
   Abstract = {Recent evidence indicates that acetylcholine and dopamine
             play complementary roles in cognitive as well as motor
             functions. In our previous study, the dopamine receptor
             blocker, haloperidol, was found to attenuate the radial-arm
             maze choice accuracy deficit caused by the muscarinic
             acetylcholine receptor blocker, scopolamine. Haloperidol has
             activity in blocking both D1 and D2 dopamine receptor
             subtypes. The current study was conducted to determine
             whether this dopamine-acetylcholine interaction specifically
             involved D1 or D2 dopamine receptors. The D1 antagonist, SCH
             23390, and the D2 antagonist, raclopride, were administered
             with a dose of scopolamine which caused choice accuracy
             deficits in the radial-arm maze. The scopolamine-induced
             deficit was reversed by SCH 23390, the D1 antagonist,
             indicating that D1 blockade alone is sufficient to reverse
             the amnestic effects of muscarinic blockade. There was no
             indication in this study that the D2 blocker, raclopride,
             had a similar effect. However, this does not mean that such
             an effect may not be present at other doses of raclopride or
             with other D2 antagonists. The present finding that D1
             blockade counteracts scopolamine-induced cognitive
             dysfunction not only furthers the understanding of
             dopamine-acetylcholine relationships in cognitive function,
             it also suggests a promising direction for the development
             of treatments for cognitive dysfunction due to cholinergic
             loss.},
   Doi = {10.1016/s0163-1047(88)90911-9},
   Key = {fds274459}
}

@article{fds274460,
   Author = {Gunne, LM and Häggström, JE and Johansson, P and Levin, ED and Terenius, L},
   Title = {Neurobiochemical changes in tardive dyskinesia.},
   Journal = {L'Encephale},
   Volume = {14 Spec No},
   Pages = {167-173},
   Year = {1988},
   Month = {September},
   ISSN = {0013-7006},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2463901},
   Keywords = {Animals • Antipsychotic Agents • Apomorphine
             • Cebus • Dyskinesia, Drug-Induced • Rats
             • Substance P • Substantia Nigra • drug
             effects • etiology • gamma-Aminobutyric Acid
             • metabolism • physiology • physiopathology*
             • toxicity},
   Abstract = {There is evidence for the view that both up- and
             downregulation of nigral GABA may give rise to dyskinetic
             movements. Intranigral infusion of GABA agonists causes
             stereotyped licking and gnawing in rats, while intranigral
             GABA antagonists produce vacuous chewing movements. It is
             hypothesized that during long-term neuroleptic treatment
             there may be a succession of changes within striatonigral
             GABA neurons: down-regulation caused by neuroleptic drugs
             may increase receptor sensitivity, and this may lead to
             overcompensation and withdrawal dyskinesia during periods of
             cessation of drug treatment. Reduced nigral GAD activity may
             be a marker of irreversible brain damage and has not been
             observed in all chronic experiments, but only in individuals
             with long-standing or irreversible dyskinesia. Changes
             within the GABA system seem to be accompanied by changes in
             the striatal and nigral levels of substance
             P.},
   Key = {fds274460}
}

@article{fds274422,
   Author = {Levin, ED and Schneider, ML and Ferguson, SA and Schantz, SL and Bowman,
             RE},
   Title = {Behavioral effects of developmental lead exposure in rhesus
             monkeys.},
   Journal = {Developmental Psychobiology},
   Volume = {21},
   Number = {4},
   Pages = {371-382},
   Year = {1988},
   Month = {May},
   ISSN = {0012-1630},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/3378682},
   Keywords = {Animals • Animals, Newborn • Attention •
             Behavior, Animal • Exploratory Behavior • Female
             • Lead • Lead Poisoning • Macaca mulatta
             • Male • Visual Perception • drug effects
             • drug effects* • pharmacokinetics •
             psychology*},
   Abstract = {Postnatal lead exposure has been found to cause long-term
             learning and memory deficits in monkeys. Pulse-chronic
             exposure, consisting of acute high-level exposure followed
             by chronic lower-level exposure, has been particularly
             effective in causing these impairments. We investigated
             possible antecedents of lead-induced cognitive dysfunction
             by evaluating the behavioral effects of pulse-chronic lead
             exposure in rhesus monkeys during the first 6 months of
             postnatal life. Blood lead concentrations in the monkeys
             reached a peak of 55.8 +/- 7.8 ug/dl during week 5 after
             birth and then averaged between 33.1 and 42.9 ug/dl during
             the rest of the first 6 months after birth. Zinc
             protoporphyrin levels were increased by lead exposure, but
             hematocrits were unaffected. Significant lead-related
             effects were detected on a visual exploration test and a
             neonatal behavioral assessment battery. Lead-treated monkeys
             exhibited decreased looking behavior on the visual
             exploration test and decreased muscle tonus and increased
             arousal or agitation on the behavioral assessment battery.
             No effects were seen on a Piagetian object permanence task
             and no toxic effects on health or growth were detected. In
             addition to providing indices of behavioral dysfunction
             during postnatal lead exposure, performance on these early
             behavioral tests may predict later lead-induced cognitive
             dysfunction.},
   Doi = {10.1002/dev.420210408},
   Key = {fds274422}
}

@article{fds274377,
   Author = {McGurk, SR and Levin, ED and Butcher, LL},
   Title = {Cholinergic-dopaminergic interactions in radial-arm maze
             performance.},
   Journal = {Behavioral and Neural Biology},
   Volume = {49},
   Number = {2},
   Pages = {234-239},
   Year = {1988},
   Month = {March},
   ISSN = {0163-1047},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/3365189},
   Keywords = {Acetylcholine • Animals • Discrimination Learning
             • Dopamine • Female • Haloperidol • Rats
             • Rats, Inbred Strains • Scopolamine • drug
             effects • pharmacology • physiology*},
   Abstract = {Although acetylcholine and dopamine are believed to play
             complementary roles in motor function, a comparable
             neurochemical interaction has not been established for
             cognitive function. The muscarinic receptor blocker
             scopolamine and the dopaminergic antagonist haloperidol have
             been found to impair choice accuracy of rats in the
             radial-arm maze. In the present study, low doses of these
             two drugs were administered intraperitoneally either alone
             or in combination to rats trained on a working memory task
             (food reward) in an eight-arm radial maze. Scopolamine,
             0.125 mg/kg, produced a significant decrease in choice
             accuracy (i.e., arm entries until an error). Haloperidol,
             0.0625 mg/kg, did not cause a significant decrease in
             accuracy, but there was a trend in that direction. The
             combination of haloperidol with scopolamine attenuated
             significantly the amnestic effect of scopolamine. These
             results suggest that, like motor behavior, cognitive
             function may be influenced by the balance between
             acetylcholine and dopamine.},
   Doi = {10.1016/s0163-1047(88)90539-0},
   Key = {fds274377}
}

@article{fds274206,
   Author = {Ellison, G and Johansson, P and Levin, E and See, R and Gunne,
             L},
   Title = {Chronic neuroleptics alter the effects of the D1 agonist
             SK&F 38393 and the D2 agonist LY171555 on oral movements in
             rats.},
   Journal = {Psychopharmacology},
   Volume = {96},
   Number = {2},
   Pages = {253-257},
   Year = {1988},
   ISSN = {0033-3158},
   url = {http://dx.doi.org/10.1007/bf00177570},
   Abstract = {Vacuous oral movements (OMs) in rats chronically
             administered haloperidol (HAL), fluphenazine (FLU), or no
             drug were studied following injections of one of three doses
             of either a D1 agonist (SK&F 38393) or a D2 agonist
             (LY171555). Oral movements were observed via closed-circuit
             television and simultaneously recorded using a computerized
             video analysis system which measured the distance between
             two fluorescent dots painted above and below the rat's
             mouth. SK&F 38393 induced a dose-dependent increase in
             tremorous oral movements and repetitive chewing movements in
             the controls; this effect was more pronounced in rats
             treated with chronic HAL or FLU, both during chronic
             neuroleptic treatment and even more so when they were tested
             after drug withdrawal following 5 or 14 months of chronic
             neuroleptic administration. Conversely, LY171555 produced an
             inhibition of oral activity at all dose levels in controls.
             This inhibition was attenuated during chronic administration
             of HAL or FLU, but returned to control levels (without any
             signs of supersensitivity) when the animals were retested
             shortly after discontinuation of neuroleptics. These results
             indicate that heightened oral movements in rodents following
             chronic neuroleptic administration can be more clearly
             induced by D1 than by D2 receptor activation.},
   Doi = {10.1007/bf00177570},
   Key = {fds274206}
}

@article{fds274355,
   Author = {Levin, ED and Ellison, GD and Salem, C and Jarvik, M and Gritz,
             E},
   Title = {Behavioral effects of acute hexamethonium in rats
             chronically intoxicated with nicotine.},
   Journal = {Physiology & Behavior},
   Volume = {44},
   Number = {3},
   Pages = {355-359},
   Year = {1988},
   ISSN = {0031-9384},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2906149},
   Keywords = {Animals • Arousal • Behavior, Animal •
             Drinking • Eating • Female • Grooming •
             Hexamethonium • Hexamethonium Compounds • Nicotine
             • Rats • Rats, Inbred Strains • Receptors,
             Nicotinic • Smell • Sympathetic Nervous System
             • drug effects • drug effects* •
             pharmacology* • toxicity*},
   Abstract = {To investigate the effects of chronic nicotine
             administration on feeding behavior, hexamethonium, a
             nicotinic blocker with mainly peripheral actions, was
             acutely given to rats during and after chronic nicotine
             administration. Nicotine decreased both the time spent
             investigating the food and the amount of food consumed. It
             also decreased the time spent rearing and grooming and
             increased the time spent resting. These behaviors returned
             to control levels after nicotine withdrawal. During nicotine
             administration, 10 mg/kg of hexamethonium increased the
             amount of time the nicotine-treated rats spent investigating
             the food but did not change the amount of food actually
             eaten. These data show that predominantly peripheral
             nicotinic blockade can partially alleviate the effects of
             chronic nicotine administration of feeding behavior,
             suggesting that at least some of the effects of nicotine on
             feeding are peripheral. The finding that the investigational
             and consummatory aspects of feeding behavior can be
             pharmacologically differentiated implies that some aspects
             of their neural control may be distinct.},
   Doi = {10.1016/0031-9384(88)90037-6},
   Key = {fds274355}
}

@article{fds274427,
   Author = {Levin, ED},
   Title = {Psychopharmacological effects in the radial-arm
             maze.},
   Journal = {Neuroscience and Biobehavioral Reviews},
   Volume = {12},
   Number = {2},
   Pages = {169-175},
   Year = {1988},
   ISSN = {0149-7634},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2902540},
   Keywords = {Animals • Brain • Discrimination Learning •
             Mental Recall • Neurotransmitter Agents •
             Orientation • Rats • Receptors, Neurotransmitter
             • drug effects • drug effects* •
             physiology*},
   Abstract = {The radial-arm maze (RAM) has become a very widely used
             method for assessing spatial memory in rodents. It has
             proven to be quite useful in the investigation of the
             effects of a variety of pharmacological manipulations on
             spatial memory. The cholinergic system has been found to be
             crucial for accurate RAM performance. Blockade of either
             muscarinic or nicotinic receptors impairs performance. Other
             transmitter systems such as dopamine and the opiates have
             also been found to be involved with the maintenance of
             accurate RAM performance. This test has been found to be
             sensitive to the effects of a variety of toxicants given
             either in adulthood or during development. These findings
             provide a background for the assessment of the effects of
             novel substances on RAM performance as well as the basis for
             the further understanding of the neural substrates of
             memory.},
   Doi = {10.1016/s0149-7634(88)80008-3},
   Key = {fds274427}
}

@article{fds274494,
   Author = {Levin, ED and Schantz, SL and Bowman, RE},
   Title = {Delayed spatial alternation deficits resulting from
             perinatal PCB exposure in monkeys.},
   Journal = {Archives of Toxicology},
   Volume = {62},
   Number = {4},
   Pages = {267-273},
   Year = {1988},
   ISSN = {0340-5761},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/3149182},
   Keywords = {Animals • Birth Weight • Female • Learning
             • Macaca mulatta • Male • Memory •
             Polychlorinated Biphenyls • Pregnancy • Prenatal
             Exposure Delayed Effects • drug effects • drug
             effects* • toxicity*},
   Abstract = {Monkeys exposed to low, chronic levels of polychlorinated
             biphenyls (PCBs) in utero and during nursing until 4 months
             after birth were tested at 4-6 years of age on delayed
             spatial alternation (DSA), a spatial learning and memory
             task. Deficits in performance accuracy were detected in two
             cohorts of monkeys whose mothers had been fed 2.5 ppm of the
             PCB mixture, Aroclor 1248, in their diet for an 18-month
             period ending at least 12 months prior to pregnancy. The
             deficit was most apparent at the shorter delays, suggesting
             that it was not due to memory impairment, but may have been
             due to impairments in associational or attentional
             processes. There may also have been a deficit in a group of
             monkeys whose mothers were fed 1.0 ppm of the PCB mixture,
             Aroclor 1016. However, the deficit in this group was less
             pronounced than in the other groups. The appearance of a
             PCB-induced cognitive deficit more than 3 years after the
             end of exposure indicated the existence of very long-term
             adverse consequences of low-level perinatal PCB
             exposure.},
   Doi = {10.1007/bf00332486},
   Key = {fds274494}
}

@article{fds274510,
   Author = {See, RE and Levin, ED and Ellison, GD},
   Title = {Characteristics of oral movements in rats during and after
             chronic haloperidol and fluphenazine administration.},
   Journal = {Psychopharmacology},
   Volume = {94},
   Number = {3},
   Pages = {421-427},
   Year = {1988},
   ISSN = {0033-3158},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/3128820},
   Keywords = {Animals • Female • Fluphenazine • Haloperidol
             • Mouth • Movement • Rats • Rats, Inbred
             Strains • Substance Withdrawal Syndrome • analogs
             & derivatives • drug effects* • pharmacology*
             • physiopathology},
   Abstract = {Rats were chronically administered either haloperidol (HAL)
             or fluphenazine (FLU) via depot injections for 8 months,
             given these same drugs in their drinking water for the next
             2 months, and then withdrawn from the drugs. Throughout the
             experiment the animals were tested repeatedly in an enclosed
             tube using a computerized device which measured
             computer-scored movelets (CSMs) and, in the latter half of
             the experiment, were also scored by a human observer in the
             tube, as well as in an open cage, for observed oral
             movements (OMs). In the tube, the animals in both
             neuroleptic-treated groups showed initial decreases in the
             number of CSMs and made sluggish CSMs; these effects were
             generally larger in the FLU animals. After 6 months of
             chronic neuroleptics, the HAL-treated animals showed
             increased oral movements, both as reported by the human
             observer and in CSMs of all amplitudes, and this effect
             increased upon drug withdrawal. FLU-treated animals showed a
             more persistent depression of both OMs and CSMs of large
             amplitudes. However, the behavior most characteristic of
             both neuroleptic-treated groups was the gradual development
             of increases in CSMs of the smallest amplitudes measurable.
             A different pattern was observed in the open cage test,
             where both neuroleptic groups showed significant increases
             in vacuous OMs during drug administration which rapidly
             became attenuated upon drug withdrawal. These results
             indicate a complex syndrome of oral activity in the drugged
             animals which changed over time. The measure of oral
             activity which most clearly showed the time-course for
             late-onset changes in oral activity was CSMs of the smallest
             amplitudes.},
   Doi = {10.1007/bf00174701},
   Key = {fds274510}
}

@article{fds274386,
   Author = {Levin, ED and Uemura, E and DeLuna, R and Franks, P and Bowman,
             RE},
   Title = {Neurobehavioral effects of chronic halothane exposure during
             developmental and juvenile periods in the
             rat.},
   Journal = {Experimental Neurology},
   Volume = {98},
   Number = {3},
   Pages = {584-593},
   Year = {1987},
   Month = {December},
   ISSN = {0014-4886},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/3678434},
   Keywords = {Aging • Animals • Behavior, Animal • Female
             • Halothane • Hippocampus • Male •
             Pregnancy • Rats • Rats, Inbred Strains •
             Synapses • drug effects • drug effects* •
             growth & development • pharmacology* •
             physiology},
   Abstract = {Chronic exposure of rats to the surgical anesthetic agent
             halothane during development has been found to cause both
             neural and behavioral impairment. Among the
             halothane-induced deficits are retarded synaptogenesis and
             impaired spontaneous alternation. It is unclear how long
             after birth the susceptibility to the neurotoxic effects of
             halothane persists. The present study compared in rats the
             effects of halothane exposure on synaptic density and
             spontaneous alternation during early and late periods of
             maturation. All three experimental groups were exposed to
             100 parts per million of halothane for 8 h/day, 5 days/week.
             One group (early exposure) was exposed from day 2 of
             conception until 30 days after birth. The second group (late
             exposure) was exposed to the same amounts from day 31 until
             day 90 after birth. The third group (continued exposure)
             received both periods. The control group was treated in the
             same way, but was not exposed to halothane. As found in the
             previous study, there were greater effects of halothane on
             synaptogenesis than on spontaneous alternation; impairment
             of spontaneous alternation behavior was found only with the
             early exposure. Deficits in synaptic density were found with
             both early and late exposure, although the early exposure
             had more severe effects. Halting the exposure to halothane
             on day 30 reinstated control-like rates of synaptogenesis,
             but the deficit in synaptic density from the early exposure
             persisted into adulthood. The potent neurotoxic effect of
             halothane in suppressing synaptogenesis highlights not only
             its potential as a hazard but also its potential as an
             experimental tool for manipulating the rate of
             synaptogenesis and examining the relationship between
             synaptic development and behavioral maturation.},
   Doi = {10.1016/0014-4886(87)90267-6},
   Key = {fds274386}
}

@article{fds274366,
   Author = {Levy, AD and See, RE and Levin, ED and Ellison, GD},
   Title = {Neuroleptic-induced oral movements in rats: methodological
             issues.},
   Journal = {Life Sciences},
   Volume = {41},
   Number = {12},
   Pages = {1499-1506},
   Year = {1987},
   Month = {September},
   ISSN = {0024-3205},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2887997},
   Keywords = {Animals • Antipsychotic Agents • Dyskinesia,
             Drug-Induced • Female • Fluphenazine •
             Haloperidol • Methods • Mouth • Movement
             • Rats • drug effects* • etiology •
             pharmacology • pharmacology* •
             physiology},
   Abstract = {In three separate experiments groups of rats were
             chronically administered neuroleptics in a variety of ways
             (chronic injections, subcutaneous implants, and decanoate
             injections) and examined for oral movements (OMs) in two
             different tests: in an open cage using a human observer, or
             in a plexiglas tube enclosure, where OMs were monitored both
             by a human observer and computerized video analysis system.
             These two testing methods showed different effects of
             neuroleptic administration. In the open cage, OMs tended to
             be enhanced during chronic neuroleptic exposure and to
             rapidly subside upon drug withdrawal. The enhanced OMs were
             especially present just after drug injections, when activity
             levels were low. In the observation tube environment,
             however, OMs tended to be low soon after drug treatments,
             and elevated upon withdrawal. Thus, the type of behavioral
             test used determines how neuroleptic-induced increases in
             oral activity should be interpreted.},
   Doi = {10.1016/0024-3205(87)90715-6},
   Key = {fds274366}
}

@article{fds274472,
   Author = {Levin, ED and Castonguay, M and Ellison, GD},
   Title = {Effects of the nicotinic receptor blocker mecamylamine on
             radial-arm maze performance in rats.},
   Journal = {Behavioral and Neural Biology},
   Volume = {48},
   Number = {2},
   Pages = {206-212},
   Year = {1987},
   Month = {September},
   ISSN = {0163-1047},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2823791},
   Keywords = {Animals • Appetitive Behavior • Brain •
             Choice Behavior • Discrimination Learning •
             Dose-Response Relationship, Drug • Female •
             Mecamylamine • Motivation • Orientation •
             Rats • Rats, Inbred Strains • Receptors, Nicotinic
             • Synaptic Transmission • drug effects • drug
             effects* • pharmacology*},
   Abstract = {Lesions of cholinergic neurons have been found by many
             investigators to impair choice accuracy in the radial arm
             maze. Because muscarinic receptor blockers, such as
             scopolamine, have also repeatedly been found to impair
             choice accuracy in the radial-arm maze, it has generally
             been thought that the critical effect of cholinergic lesions
             is the deafferentation of muscarinic receptors. The possible
             involvement of nicotinic receptors in the cholinergic bases
             of cognitive performance in the radial-arm maze has not been
             as well investigated. The present study examined the effects
             of the blockade of nicotinic receptors on performance of
             female Sprague-Dawley rats in the radial-arm maze. Acute
             administration of the the nicotinic receptor blocker,
             mecamylamine (10 mg/kg) was found to significantly impair
             radial-arm maze choice accuracy. This dose also caused a
             significant increase in response latency in the maze. The
             effect on choice behavior but not locomotor speed seemed to
             be due to the central effects of mecamylamine, because
             administration of the peripheral nicotine receptor blocker,
             hexamethonium (20 mg/kg), did not impair choice accuracy,
             even though it did increase response latency to a similar
             degree as the 10-mg/kg dose of mecamylamine. Lower doses of
             mecamylamine (2.5 and 5 mg/kg) did not impair choice
             accuracy. These results indicate that central nicotinic as
             well as muscarinic cholinergic receptors are involved with
             cognitive functioning.},
   Doi = {10.1016/s0163-1047(87)90752-7},
   Key = {fds274472}
}

@article{fds274483,
   Author = {Morgan, MM and Levin, ED and Liebeskind, JC},
   Title = {Characterization of the analgesic effects of the
             benzodiazepine antagonist, Ro 15-1788.},
   Journal = {Brain Research},
   Volume = {415},
   Number = {2},
   Pages = {367-370},
   Year = {1987},
   Month = {July},
   ISSN = {0006-8993},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/3111641},
   Keywords = {Analgesics • Animals • Diazepam • Flumazenil
             • Male • Naloxone • Rats • Rats, Inbred
             Strains • antagonists & inhibitors • pharmacology
             • pharmacology*},
   Abstract = {Three experiments were carried out in rats to evaluate the
             analgesic effects of the benzodiazepine antagonist, Ro
             15-1788. Expt. 1 demonstrated a diazepam reversible
             analgesic effect of Ro 15-1788 using the tail-flick test.
             Expt. 2 analyzed the effects of Ro 15-1788 in the hot-plate
             test at various doses. Low doses of Ro 15-1788 proved
             analgesia 20 min after drug injection, whereas high doses
             had no analgesic effect on the 20 min test, but were
             effective on the 50 min test. Expt. 3 demonstrated that the
             opiate antagonist, naloxone, had no effect on analgesia
             produced by Ro 15-1788 in the hot-plate test. The analgesic
             effects of Ro 15-1788 may be attributable to its reported
             anxiogenic properties.},
   Doi = {10.1016/0006-8993(87)90222-8},
   Key = {fds274483}
}

@article{fds274329,
   Author = {Johansson, P and Levin, E and Gunne, L and Ellison,
             G},
   Title = {Opposite effects of a D1 and a D2 agonist on oral movements
             in rats.},
   Journal = {European Journal of Pharmacology},
   Volume = {134},
   Number = {1},
   Pages = {83-88},
   Year = {1987},
   Month = {January},
   ISSN = {0014-2999},
   url = {http://dx.doi.org/10.1016/0014-2999(87)90134-8},
   Abstract = {Oral movements in rats administered one of three doses of
             either a D1 agonist (SK&F 38393) or a D2 agonist (LY171555)
             were observed via closed-circuit television and
             simultaneously recorded using a computerized video analysis
             system which measured the distance between two fluorescent
             dots painted above and below the rat's mouth. The D1 agonist
             SK&F 38393 induced a dose-dependent increase in tremorous
             oral movements, tongue protrusions, and, at the highest
             dose, increased repetitive chewing movements. Conversely,
             the D2 agonist LY171555 produced an inhibition or oral
             activity at all dose levels. At the lowest dose tested this
             appeared to reflect a non-specific decrease in activity, for
             there was an inhibition of all categories of behavior
             measured, as well as of all amplitudes of computer-scored
             movements and slow, sluggish movements were recorded. But
             higher doses of LY171555 induced hyperactivity and
             stereotyped, repetitive head movements whereas chewing
             movements, tremorous oral movements, and tongue protrusions
             were still decreased. D1 and D2 dopamine receptors appear to
             have opposite effects on oral movements.},
   Doi = {10.1016/0014-2999(87)90134-8},
   Key = {fds274329}
}

@article{fds274362,
   Author = {Levin, ED and Galen, DM and Ellison, GD},
   Title = {Chronic haloperidol effects on oral movements and radial-arm
             maze performance in rats.},
   Journal = {Pharmacology, Biochemistry, and Behavior},
   Volume = {26},
   Number = {1},
   Pages = {1-6},
   Year = {1987},
   Month = {January},
   ISSN = {0091-3057},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/3562481},
   Keywords = {Animals • Choice Behavior • Dyskinesia,
             Drug-Induced • Female • Haloperidol • Memory
             • Motor Activity • Mouth • Rats • drug
             effects • drug effects* • toxicity*},
   Abstract = {Rats were examined for the development of adverse motor and
             cognitive effects during and after 24 weeks of chronic
             haloperidol (HAL) administration using an 8-arm maze and a
             computerized apparatus for measuring spontaneous oral
             movements. In the maze, HAL caused a significant decline in
             choice accuracy only during the first week of
             administration, whereas it caused a significant decline in
             locomotor speed throughout drug administration. There were
             no effects of HAL on maze behavior after withdrawal.
             Haloperidol reduced the number of mouth movements during
             drug administration, but after withdrawal there was a
             significant increase. This replicated a previous finding
             from our lab. The oral movements which did occur in the
             HAL-treated rats were slower than normal. The timing of the
             HAL-induced cognitive dysfunction was similar to the
             Parkinson-like disorder shown by patients given chronic
             neuroleptics, whereas the timing of the increase in oral
             movements after the withdrawal of HAL was more related to
             the appearance of tardive dyskinesia. There was evidence in
             both tests of a persisting sedation during chronic
             neuroleptic administration.},
   Doi = {10.1016/0091-3057(87)90523-5},
   Key = {fds274362}
}

@article{fds274330,
   Author = {Ellison, G and See, R and Levin, E and Kinney, J},
   Title = {Tremorous mouth movements in rats administered chronic
             neuroleptics.},
   Journal = {Psychopharmacology},
   Volume = {92},
   Number = {1},
   Pages = {122-126},
   Year = {1987},
   ISSN = {0033-3158},
   url = {http://dx.doi.org/10.1007/bf00215492},
   Abstract = {Oral movements (OMs) in rats administered chronic
             haloperidol (HAL) were quantified simultaneously by a human
             observer and via a computerized video analysis system which
             monitored the distance between the upper and low lips using
             TV images. The human observer data indicated that during HAL
             administration the total duration of OMs was initially
             decreased, gradually returned to levels slightly above
             controls, and then increased substantially upon drug
             withdrawal. The computer records confirmed these findings
             and further indicated that after prolonged HAL
             administration a syndrome developed in which large-amplitude
             OMs remained suppressed but OMs of the smallest detectable
             amplitudes increased. Upon drug withdrawal, these small OMs
             increased in amplitude and rhythmicity, developing into
             repetitive tremors.},
   Doi = {10.1007/bf00215492},
   Key = {fds274330}
}

@article{fds274413,
   Author = {Levin, ED and Morgan, MM and Galvez, C and Ellison,
             GD},
   Title = {Chronic nicotine and withdrawal effects on body weight and
             food and water consumption in female rats.},
   Journal = {Physiology & Behavior},
   Volume = {39},
   Number = {4},
   Pages = {441-444},
   Year = {1987},
   ISSN = {0031-9384},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/3575490},
   Keywords = {Animals • Body Weight • Drinking Behavior •
             Drug Tolerance • Feeding Behavior • Female •
             Nicotine • Rats • Rats, Inbred Strains •
             Substance Withdrawal Syndrome • drug effects* •
             pharmacology* • physiopathology*},
   Abstract = {Female rats were used to examine the effects of chronic
             nicotine administration and withdrawal on food and water
             consumption and body weight. Rats with chronic nicotine
             pellet implants consumed significantly less food and water
             than controls for the first five days and then gradually
             returned to control levels of consumption. The lowest level
             of body weight was reached on day 9 after which there was a
             slow return to control weights by day 21. When the nicotine
             pellets were removed from the short-term exposure group on
             day 14, they showed significant hyperphagia and hyperdipsia
             and a very rapid weight gain for the next several days,
             which clearly outpaced the recovery of weight in the
             long-term nicotine exposure group. These results show that
             in female rats changes in weight during chronic nicotine
             administration and withdrawal are accompanied by changes in
             rates of consumption. In addition, nicotine withdrawal can
             cause hyperphagia and hyperdipsia even though levels of
             consumption had previously returned to control levels and
             even though the route of nicotine administration was not
             oral.},
   Doi = {10.1016/0031-9384(87)90370-2},
   Key = {fds274413}
}

@article{fds274452,
   Author = {Lubischer, JL and See, RE and Levin, ED and Liebeskind,
             JC},
   Title = {The effects of D1 and D2 receptor antagonists on pain
             sensitivity and morphine analgesia in the
             rat.},
   Journal = {Proceedings of the Western Pharmacology Society},
   Volume = {30},
   Pages = {229-232},
   Year = {1987},
   ISSN = {0083-8969},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/3306694},
   Keywords = {(R)-2,3,4,5-Tetrahydro-8-chloro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol
             • Animals • Benzazepines • Male •
             Morphine • Pain • Rats • Rats, Inbred Strains
             • Receptors, Dopamine • Sulpiride • drug
             effects* • pharmacology • pharmacology* •
             physiopathology*},
   Key = {fds274452}
}

@article{fds274466,
   Author = {Levin, ED and Bowman, RE and Wegert, S and Vuchetich,
             J},
   Title = {Psychopharmacological investigations of a lead-induced
             long-term cognitive deficit in monkeys.},
   Journal = {Psychopharmacology},
   Volume = {91},
   Number = {3},
   Pages = {334-341},
   Year = {1987},
   ISSN = {0033-3158},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/3104955},
   Keywords = {Acetylcholine • Amphetamine • Animals •
             Behavior, Animal • Cognition Disorders • Dopamine
             • Haloperidol • Lead Poisoning • Levodopa
             • Macaca mulatta • Physostigmine •
             Scopolamine • Sulpiride • chemically induced*
             • drug effects • pharmacology • physiology
             • psychology*},
   Abstract = {This study investigated pharmacological manipulations of the
             cholinergic (ACh) and dopaminergic (DA) transmitter systems
             in monkeys with a long-term lead-induced cognitive deficit
             on delayed spatial alternation (DSA). Both ACh and DA have
             been found to be affected by developmental lead exposure and
             to be involved with performance on spatial learning and
             memory tasks. The lead-induced deficit in performance
             accuracy on DSA persisted throughout the 2 years of this
             experiment, which ended more than 8 years after the end of
             the postnatal lead exposure. Acute administration of
             agonists and antagonists of the ACh and DA systems did not
             elicit differential effects from the lead-exposed and
             control groups in terms of DSA per cent correct performance.
             The ACh antagonist, scopolamine, caused a dose-related
             decline in performance in both groups. Significant
             amelioration of the lead-induced DSA deficit was achieved by
             chronic treatment with the DA agonist, L-dopa. After
             withdrawal from L-dopa, the lead-related deficit reappeared.
             Improvement in performance of the lead-treated group was
             also seen after chronic amphetamine administration, but this
             effect was not significant. These data implicate DA
             mechanisms in the long-lasting cognitive effects of
             developmental lead exposure. The alleviation of the deficit
             with chronic administration of a DA precursor points to a
             possible line of treatment for the cognitive effects of
             developmental lead exposure.},
   Doi = {10.1007/bf00518187},
   Key = {fds274466}
}

@article{fds274463,
   Author = {Levin, ED and Bowman, RE},
   Title = {Effects of the dopamine D-2 receptor agonist, LY 171555, on
             radial arm maze performance in rats.},
   Journal = {Pharmacology, Biochemistry, and Behavior},
   Volume = {25},
   Number = {5},
   Pages = {1117-1119},
   Year = {1986},
   Month = {November},
   ISSN = {0091-3057},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2947250},
   Keywords = {Animals • Cognition • Ergolines • Learning
             • Male • Quinpirole • Rats • Rats,
             Inbred Strains • Receptors, Dopamine • Receptors,
             Dopamine D2 • drug effects • drug effects* •
             pharmacology*},
   Abstract = {Rats trained to run through an 8-arm radial maze for food
             reinforcement were injected with a broad range of doses of
             the dopamine D-2 receptor agonist, LY 171555. Deficits were
             detected by the choice measures of entries to repeat and
             arms entered in the first eight choices. There was a
             dose-related increase in latency to finish the maze even
             though there was no significant increase in the number of
             choices needed to finish the maze.},
   Doi = {10.1016/0091-3057(86)90095-x},
   Key = {fds274463}
}

@article{fds274424,
   Author = {Levin, ED and Bowman, RE},
   Title = {Behavioral effects of chronic exposure to low concentrations
             of halothane during development in rats.},
   Journal = {Anesthesia and Analgesia},
   Volume = {65},
   Number = {6},
   Pages = {653-659},
   Year = {1986},
   Month = {June},
   ISSN = {0003-2999},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/3706802},
   Keywords = {Analysis of Variance • Animals • Body Weight
             • Escape Reaction • Female • Halothane •
             Learning • Male • Maternal-Fetal Exchange •
             Pregnancy • Psychomotor Performance • Rats •
             Rats, Inbred Strains • Startle Reaction • drug
             effects • drug effects* • pharmacology*},
   Abstract = {Long-term behavioral effects of chronic exposure to low
             concentrations of halothane were evaluated in rats exposed
             to low (12.5 ppm) concentrations from day 2 of conception
             until either 30 (halothane-30) or 60 (halothane-60) days
             after birth. Rats similarly treated but not exposed to
             halothane served as controls. When these rats were tested
             for radial arm maze exploration as adults (1 yr old) both
             exposure groups showed significant deficits compared with
             controls. The halothane-treated rats entered significantly
             fewer arms before reentering an arm (entries-to-repeat). At
             55 days of age, in the spontaneous alternation test,
             response speed was significantly slower than controls in
             both halothane-30 and halothane-60 rats. This effect was not
             seen in rats more than 55 days old. Replicating previous
             results, the halothane-60 rats showed deficits in learning a
             light-dark discrimination. This deficit was not seen with
             halothane-30 rats, indicating that continued halothane
             exposure during the 30- through 60-day period was necessary
             for inducing a noticeable long-term learning deficit. The
             results show that chronic exposure of rats to low
             concentrations of halothane during development results in
             subsequent behavioral alteration, and that termination of
             halothane exposure at 30 days of age rather than at 60 days
             of age avoids some of the signs of behavioral
             impairment.},
   Key = {fds274424}
}

@article{fds274458,
   Author = {Levin, ED and Bowman, RE},
   Title = {Long-term lead effects on the Hamilton Search Task and
             delayed alt