Office Location: | 323 Foster St, Durham, NC 27701 |
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Ph.D. | University of Wisconsin, Madison | 1984 |
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
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.