Research Interests for Edward D. Levin

Dr. Levin a Professor in the Department of Psychiatry and Behavioral Sciences at Duke University Medical Center, with joint appointments in the Departments of Psychology and Pharmacology as well as the School of the Environment. The primary research effort of his laboratory is to understand neurobehavioral interactions underlying cognitive function and reinforcement and to apply this knowledge to better understand cognitive dysfunction and addiction to develop novel therapeutic treatments. The centerpiece of his research is directed to understand the basic neural mechanisms of cognition and addiction. The two principal applied foci concern behavioral toxicology, the negative impact of chemical exposure, and therapeutics, development of treatments to reverse cognitive impairment and addiction. Currently, our principal research focus concerns nicotinic receptor systems and their interactions with related transmitter systems such as dopamine, serotonin, norepinepherine, GABA and glutamate. We have documented the effects of nicotine and selective nicotinic receptor subtype drugs on cognitive function including learning, memory and attention. In age effect studies we have shown that adolescents self-administer greater amounts of nicotine than adults and that particularly in females greater adolescent-onset of nicotine self-administration continues into adulthood. We have also found that prenatal nicotine exposure in females causes more persistent nicotine self-administration when they become adults. Using knockout mice, we have found that β2-containinc nicotinic receptors appear to be more important for the initiation of nicotine self-administration during the first few weeks, whereas α7 nicotinic receptors appear to be more important for the long-term consumption of nicotine over a period of 5 months. We are continuing with more mechanistic studies in rat models using selective lesions, local infusions and neurotransmitter interaction studies. We have found that nicotine improves memory performance in normal rats, and in rats with lesions of hippocampal and basal forebrain connections. We are concentrating on hippocampal α7 and α4β2 nicotinic receptor subtypes and how they interact with dopamine D1 and D2, serotonin 5HT2, GABA and glutamate NMDA systems with regard to memory, attention and nicotine self-administration. Nicotinic interactions with antipsychotic drugs and cognitive function is another focus of our lab. This line has led us to find that the 5HT2 antagonist effects of atypical antipsychotic drugs clocks nicotine-induced attentional and memory improvement. In addition to providing caution concerning the use of nicotinic agonists in the improvement of cognitive function in people with schizophrenia taking these drugs, this led us to try 5HT2 antagonist treatment to reduce nicotine self-administration. We found that ketanserin a 5HT2 antagonist does significantly reduce nicotine self-administration in rats. Now we are designing a study to try this approach in humans. In the area of neurobehavioral toxicology, we are continuing projects to characterize the adverse effects of prenatal and adolescent nicotine exposure. Our primary projects in neurobehavioral toxicology focuses on the cognitive deficits caused by pesticides such as chlorpyrifos and marine toxins such as domoic acid and ciguatera toxin. We are studying zebrafish to understand the molecular bases of toxicant-induced cognitive dysfunction and novel therapeutic treatments. The basic and applied aims of our research complement each other nicely. The findings concerning neural mechanisms underlying cognitive function and addiction help direct the behavioral toxicology and therapeutic development studies, while the applied studies provide important functional information concerning the importance of the basic mechanisms under investigation. The aim of these interacting lines of basis and applied research is understand the neural bases of cognitive function and addiction and to develop more effective therapeutic treatments.

Keywords:

1-Naphthylamine, 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine, 3,4-Dihydroxyphenylacetic Acid, Abnormalities, Drug-Induced, Acetylcholine, Acetylcholinesterase, Aconitine, Acoustic Stimulation, Actins, Acute Disease, Acyltransferases, Adaptation, Physiological, Adenylate Cyclase, Adiponectin, Adipose Tissue, Administration, Cutaneous, Administration, Oral, Adolescent, Adrenergic alpha-2 Receptor Antagonists, Adrenergic alpha-Antagonists, Adult, Aerosols, Affect, Age Factors, Age of Onset, Aged, Aged, 80 and over, Aging, Air Pollutants, Alcohol Deterrents, Alcohol Drinking, Alcoholism, Alkaloids, Allosteric Regulation, alpha-Methyltyrosine, Alzheimer Disease, Amino Acids, Amino Acids, Branched-Chain, Amphetamine, Amygdala, Anabasine, Anal Canal, Analgesics, Analysis of Variance, Animals, Animals, Newborn, Animals, Suckling, Anthelmintics, Anti-Anxiety Agents, Anti-HIV Agents, Anticonvulsants, Antidepressive Agents, Antineoplastic Agents, Hormonal, Antioxidants, Antipsychotic Agents, Anxiety, Anxiety Disorders, Apolipoproteins E, Apomorphine, Apoptosis, Appetitive Behavior, Arecoline, Aroclors, Arousal, Ascorbic Acid, Association Learning, Athetosis, Attention, Attention Deficit Disorder with Hyperactivity, Autonomic Nervous System, Autoradiography, Axons, Azepines, Azetidines, Azocines, Baclofen, Basal Ganglia, Behavior, Behavior Therapy, Behavior, Addictive, Behavior, Animal, Behavioral Symptoms, Benzamides, Benzazepines, Benzodiazepines, Binding Sites, Binding, Competitive, Biogenic Monoamines, Birth Weight, Blinking, Blood Pressure, Body Mass Index, Body Temperature, Body Temperature Regulation, Body Weight, Bone and Bones, Brain, Brain Chemistry, Brain Diseases, Breath Tests, Bridged Compounds, Bungarotoxins, Buspirone, Butyrophenones, Callithrix, Carbamates, Carbon Dioxide, Carbon Monoxide, Carbon Monoxide Poisoning, Carboxylic Acids, Carrier Proteins, Catecholamines, Catheterization, Catheters, Indwelling, Caudate Nucleus, Cebus, Cell Death, Cell Differentiation, Cell Division, Cell Proliferation, Cell Size, Cell Survival, Cells, Cultured, Central Nervous System, Central Nervous System Depressants, Central Nervous System Diseases, Central Nervous System Stimulants, Cerebellum, Cerebral Cortex, Child, Chlordiazepoxide, Chlorpyrifos, Choice Behavior, Choline O-Acetyltransferase, Cholinergic Agents, Cholinergic Antagonists, Cholinergic Fibers, Cholinergic Neurons, Cholinesterase Inhibitors, Chromatography, High Pressure Liquid, Chronic Disease, Ciguatera Poisoning, Ciguatoxins, Citrates, Citric Acid, Clozapine, Cocaine, Cocaine-Related Disorders, Cognition, Cognition Disorders, Colitis, Ulcerative, Combat Disorders, Combined Modality Therapy, Comorbidity, Computer Simulation, Conditioning (Psychology), Conditioning, Classical, Conditioning, Operant, Confounding Factors (Epidemiology), Consumer behavior, Consumer Satisfaction, Contrast Sensitivity, Corpus Striatum, Cotinine, Counseling, Critical Period (Psychology), Cross-Over Studies, Cross-Sectional Studies, Crystallography, X-Ray, Cues, Cycloserine, Cystine, Cytochrome P-450 Enzyme System, Darkness, Data Collection, Data Interpretation, Statistical, Death, Sudden, Decision Making, Delayed-Action Preparations, Dendrites, Denervation, Dentate Gyrus, Depression, Depressive Disorder, Dexamethasone, Dextroamphetamine, Diabetes, Diazepam, Diazinon, Diet, Diet, Carbohydrate-Restricted, Diet, High-Fat, Dietary Fats, Dietary Sucrose, Dihydro-beta-Erythroidine, Dinoflagellida, Discrimination (Psychology), Discrimination Learning, Disease Models, Animal, Diving, Dizocilpine Maleate, DNA, DNA Fragmentation, DNA Replication, Dopamine, Dopamine Agents, Dopamine Agonists, Dopamine Antagonists, Dopamine Plasma Membrane Transport Proteins, Dopamine Uptake Inhibitors, Dopaminergic Neurons, Dose-Response Relationship, Drug, Dose-Response Relationship, Radiation, Double-Blind Method, Down-Regulation, Drinking, Drinking Behavior, Drive, Drug Administration Schedule, Drug Antagonism, Drug Combinations, Drug Delivery Systems, Drug Design, Drug Discovery, Drug Evaluation, Preclinical, Drug Implants, Drug Interactions, Drug Partial Agonism, Drug Synergism, Drug Therapy, Combination, Drug Tolerance, Drug Toxicity, Drugs, Investigational, Dyskinesia, Drug-Induced, Eating, Embryo, Nonmammalian, Embryonic Development, Emotions, Energy Metabolism, Environmental Exposure, Environmental Pollutants, Environmental Pollution, Enzyme Activation, Equipment Design, Ergolines, Escape Reaction, Esters, Estrus, Ethanol, Ethology, Evaluation Studies as Topic, Excitatory Amino Acid Agonists, Excitatory Amino Acid Antagonists, Exploratory Behavior, Extinction, Psychological, Extracellular Space, Feeding Behavior, Female, Ferrets, Fetus, Fibroblasts, Fishes, Flavoring Agents, Flumazenil, Fluoxetine, Fluphenazine, Follow-Up Studies, Food, Food Deprivation, Food Preferences, Forelimb, Form Perception, Fornix, Brain, Free Radicals, Fundulidae, GABA Agonists, GABA Antagonists, GABA Modulators, Galantamine, Galvanic Skin Response, gamma-Aminobutyric Acid, Ganglionic Stimulants, Gene Expression Profiling, Gene Expression Regulation, Gene Expression Regulation, Enzymologic, Genetic Predisposition to Disease, Genetics, Genomics, Genotype, Gerbillinae, Glucocorticoids, Glutamate Decarboxylase, Glutamic Acid, Glutathione Transferase, Golgi Apparatus, Greenhouse Effect, Grooming, Habenula, Habituation, Psychophysiologic, Halogenated Diphenyl Ethers, Haloperidol, Halothane, Haplorhini, Head, Heart, Heart Rate, Hemicholinium 3, Hexamethonium, Hexamethonium Compounds, Hippocampus, Histamine, Histamine Antagonists, Histamine H1 Antagonists, Histamine H3 Antagonists, Humans, Hydrogen-Ion Concentration, Hydroxyl Radical, Hydroxylation, Hydroxymethyl and Formyl Transferases, Hyperkinesis, Hypersensitivity, Hypothermia, Hypothermia, Induced, Ibotenic Acid, Idazoxan, Imaging, Three-Dimensional, Imidazoles, Immobility Response, Tonic, Incidence, Indans, Inferior Colliculi, Infusion Pumps, Infusions, Intravenous, Infusions, Parenteral, Infusions, Subcutaneous, Inhibition (Psychology), Injections, Injections, Intraperitoneal, Injections, Intraventricular, Injections, Subcutaneous, Insecticides, Insulin, Intracellular Signaling Peptides and Proteins, Ischemic Attack, Transient, Isoflavones, Isoflurophate, Kainic Acid, Ketanserin, Ketogenic Diet, Kidney, Killer Cells, Natural, Kynurenic Acid, Larva, Lead, Lead Poisoning, Learning, Learning Disorders, Leptin, Levodopa, Ligands, Light, Lipid Metabolism, Litter Size, Liver, Lobeline, Locomotion, Long-Term Potentiation, Longitudinal Studies, Macaca mulatta, Magnetic Resonance Spectroscopy, Male, Mammals, Mass Spectrometry, Mastication, Matched-Pair Analysis, Maternal Exposure, Maternal-Fetal Exchange, Maze Learning, Mecamylamine, Mediodorsal Thalamic Nucleus, Membrane Glycoproteins, Membrane Proteins, Membrane Transport Proteins, Membranes, Memory, Memory Disorders, Memory, Short-Term, Mental Disorders, Mental Recall, Mercury Poisoning, Nervous System, Mesencephalon, Metabolic Detoxication, Phase I, Metabolic Detoxication, Phase II, Metabolic Diseases, Metallothionein, Metals, Methods, Methylphenidate, Methyltyrosines, Mianserin, mice, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Microdialysis, Microinjections, Microscopy, Electron, Microtubules, Middle Aged, Milk, Human, Models, Animal, Models, Biological, Models, Molecular, Molecular Structure, Molecular Targeted Therapy, Mood Disorders, Morphine, Motivation, Motor Activity, Mouth, Movement, Muscarinic Agonists, Muscarinic Antagonists, Muscle, Skeletal, Myocardial Infarction, Myocardium, Naloxone, Naltrexone, Nanoparticles, Narcotic Antagonists, Nebulizers and Vaporizers, Nerve Regeneration, Nerve Tissue Proteins, Nervous System, Nervous System Diseases, Nervous System Neoplasms, Neural Inhibition, Neural Pathways, Neuroblastoma, Neurochemistry, Neuromuscular Blocking Agents, Neuromuscular Depolarizing Agents, Neuronal Plasticity, Neurons, Neuropeptide Y, Neuropsychological Tests, Neurotoxicity Syndromes, Neurotoxins, Neurotransmitter Agents, Neurotransmitter Uptake Inhibitors, Nicotine, Nicotinic Acids, Nicotinic Agonists, Nicotinic Antagonists, Nitric Oxide Synthase, Noise, Nootropic Agents, Norepinephrine, Norepinephrine Plasma Membrane Transport Proteins, North Carolina, Nucleus Accumbens, Obesity, Oligonucleotide Array Sequence Analysis, Organ Size, Organ Specificity, Organic Chemicals, Organometallic Compounds, Organophosphorus Compounds, Orientation, Osmotic Pressure, Oxidative Stress, Oxidopamine, Oxotremorine, Pain, Pain Measurement, Parasympathomimetics, Parathion, Parkinson Disease, Particle Size, Particulate Matter, Patents as Topic, Patient Compliance, Pattern Recognition, Visual, PC12 Cells, Penis, Peptide Fragments, Peptides, Pergolide, Personal Satisfaction, Personality Inventory, Pesticides, Pfiesteria piscicida, Pharmaceutical Preparations, Phenanthridines, Phenelzine, Phenotype, Phenyl Ethers, Phosphinic Acids, Phosphites, Photic Stimulation, Phylogeny, Physical Exertion, Physical Stimulation, Physostigmine, Pilocarpine, Piperazines, Piperidines, Plant Extracts, Plants, Toxic, Poisons, Polybrominated Biphenyls, Polychlorinated Biphenyls, Prefrontal Cortex, Pregnancy, Prenatal Exposure Delayed Effects, Prognosis, Propranolol, Protein Binding, Protein Subunits, Protozoan Infections, Protozoan Infections, Animal, Psychiatric Status Rating Scales, Psychological Tests, Psychomotor Disorders, Psychomotor Performance, Pulmonary Heart Disease, Putamen, Pyridines, Pyrilamine, Questionnaires, Quinolizines, Quinoxalines, Quinpirole, Raclopride, Radioligand Assay, Random Allocation, Randomized Controlled Trials as Topic, rats, Rats, Rats, Inbred F344, Rats, Inbred SHR, Rats, Inbred Strains, Rats, Sprague-Dawley, Rats, Wistar, Reaction Time, Reactive Oxygen Species, Receptor Cross-Talk, Receptor, Muscarinic M2, Receptor, Serotonin, 5-HT1A, Receptor, Serotonin, 5-HT2A, Receptor, Serotonin, 5-HT2C, Receptors, Adrenergic, Receptors, Adrenergic, alpha-2, Receptors, Adrenergic, beta, Receptors, Cholinergic, Receptors, Dopamine, Receptors, Dopamine D1, Receptors, Dopamine D2, Receptors, GABA-B, Receptors, Glutamate, Receptors, Histamine H1, Receptors, Histamine H3, Receptors, Muscarinic, Receptors, N-Methyl-D-Aspartate, Receptors, Neuropeptide Y, Receptors, Neurotransmitter, Receptors, Nicotinic, Receptors, Serotonin, 5-HT2, Recognition (Psychology), Recurrence, Reference Values, Reflex, Acoustic, Regression Analysis, Reinforcement (Psychology), Reinforcement Schedule, Reproducibility of Results, Research Design, Respiratory System, Retention (Psychology), Reversal Learning, Review Literature as Topic, Reward, Risk Assessment, Risk Factors, Risperidone, RNA, Messenger, Saccharin, Salicylamides, Saliva, Schizophrenia, Schizophrenic Psychology, Scopolamine Hydrobromide, Second Messenger Systems, Seizures, Selection, Genetic, Self Administration, Self-Help Groups, Sensation, Sensory Gating, Sensory Thresholds, Serotonin, Serotonin 5-HT2 Receptor Agonists, Serotonin 5-HT2 Receptor Antagonists, Serotonin 5-HT3 Receptor Antagonists, Serotonin Agents, Serotonin Antagonists, Serotonin Plasma Membrane Transport Proteins, Serotonin Uptake Inhibitors, Sertraline, Severity of Illness Index, Sex Characteristics, Sex Differentiation, Sex Distribution, Sex Factors, Sex Preselection, Sex Ratio, Sexual Maturation, Signal Detection, Psychological, Signal Transduction, Silver, Smell, Smoke, Smoking, Smoking Cessation, Software, Space Perception, Spatial Behavior, Species Specificity, Spectrometry, Mass, Electrospray Ionization, Spiro Compounds, Spleen, Startle Reaction, Statistics as Topic, Statistics, Nonparametric, Stereotaxic Techniques, Stress, Psychological, Structure-Activity Relationship, Substance P, Substance Withdrawal Syndrome, Substance-Related Disorders, Substantia Nigra, Sulpiride, Superoxide Dismutase, Survival, Survival Rate, Swimming, Sympathectomy, Chemical, Sympathetic Nervous System, Sympatholytics, Symporters, Synapses, Synaptic Transmission, Task Performance and Analysis, Taste, Technology, Pharmaceutical, Telephone, Teratogens, Teratology, Thalamic Nuclei, Thiobarbituric Acid Reactive Substances, Time, Time Factors, Tobacco, Tobacco Products, Tobacco Use Disorder, Tongue, Toxicity Tests, Toxicology, Trachea, Transcription, Genetic, Treatment Outcome, Tremor, Tritium, Tryptophan, Tubocurarine, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha, Up-Regulation, Vagina, Ventral Tegmental Area, Veterans, Vietnam, Visual Perception, Water Pollutants, Chemical, Weight Gain, Young Adult, zebrafish, Zebrafish, Zebrafish Proteins, Zidovudine, Zinc

Current projects:

Persisting cognitive impairments of developmental pesticide exposure

Nicotinic receptor knockouts and nicotine effects on cognition and addiction

Adolescent-onset Nicotine Addiction

Zebrafish cognition and neurobehavioral pharmacology

Representative Publications   (search)

1. Levin, ED, Fetal nicotinic overload, blunted sympathetic responsivity, and obesity., Birth Defects Res A Clin Mol Teratol, vol. 73 no. 7 (July, 2005), pp. 481-484 [15959889], [doi].
2. Levin, ED; Christopher, NC; Crapo, JD, Memory decline of aging reduced by extracellular superoxide dismutase overexpression., Behav Genet, vol. 35 no. 4 (July, 2005), pp. 447-453 [15971025], [doi] [abs].
3. Addy, NA; Pocivavsek, A; Levin, ED, Reversal of clozapine effects on working memory in rats with fimbria-fornix lesions., Neuropsychopharmacology, vol. 30 no. 6 (June, 2005), pp. 1121-1127 [15688087], [doi] [abs].
4. Levin, ED; Tizabi, Y; Rezvani, AH; Caldwell, DP; Petro, A; Getachew, B, Chronic nicotine and dizocilpine effects on regionally specific nicotinic and NMDA glutamate receptor binding., Brain Res, vol. 1041 no. 2 (April, 2005), pp. 132-142 [15829222], [doi] [abs].
5. Levin, ED; Pizarro, K; Pang, WG; Harrison, J; Ramsdell, JS, Persisting behavioral consequences of prenatal domoic acid exposure in rats., Neurotoxicol Teratol, vol. 27 no. 5 (2005), pp. 719-725 [16054336], [doi] [abs].
6. Rezvani, AH; Levin, ED, Nicotine-antipsychotic drug interactions and attentional performance in female rats., Eur J Pharmacol, vol. 486 no. 2 (February, 2004), pp. 175-182 [14975706], [doi] [abs].
7. White, HK; Levin, ED, Chronic transdermal nicotine patch treatment effects on cognitive performance in age-associated memory impairment., Psychopharmacology (Berl), vol. 171 no. 4 (February, 2004), pp. 465-471 [14534771], [doi] [abs].
8. Icenogle, LM; Christopher, NC; Blackwelder, WP; Caldwell, DP; Qiao, D; Seidler, FJ; Slotkin, TA; Levin, ED, Behavioral alterations in adolescent and adult rats caused by a brief subtoxic exposure to chlorpyrifos during neurulation., Neurotoxicol Teratol, vol. 26 no. 1 (2004), pp. 95-101 [15001218], [doi] [abs].
9. Levin, ED; Chen, E, Nicotinic involvement in memory function in zebrafish., Neurotoxicol Teratol, vol. 26 no. 6 (2004), pp. 731-735 [15451037], [doi] [abs].
10. Levin, ED; Swain, HA; Donerly, S; Linney, E, Developmental chlorpyrifos effects on hatchling zebrafish swimming behavior., Neurotoxicol Teratol, vol. 26 no. 6 (2004), pp. 719-723 [15451035], [doi] [abs].
11. 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. .