This application is a re-submission of an Independent Scientist Award (K02). The candidate is Frederick G. Moeller, M.D. He is an associate professor in the Department of Psychiatry and Behavioral Sciences. Environment: He is a member of the Psychiatry Department's Substance Abuse Research Center, and has several established investigators in the area of substance abuse, laboratory measurement of behavior and neurochemistry with whom he collaborates. His Human and wet laboratories occupy approximately 2,000 square feet of space. Research Projects: The research plan draws heavily from currently funded grants R01 DA08425, and R01 AA10828 on which the author is the principal investigator. The overall aim of this proposal is to study the relationship between drug use, serotonin, and impulsive/aggressive behaviors. Once the underlying biochemistry of these behaviors is determined, this will allow development of treatments for impulsivity, which leads to behaviors such as drug use or impulsive sexual behaviors that increase the risk for HIV transmission. The proposed research is grouped into four experiments. Experiment I will determine if combining two treatments which can decrease impulsive behavior (the serotonin reuptake inhibitor citalopram and behavior modification through monetary contingencies) will improve response to treatment in cocaine dependence. Experiment II will measure ethanol induced aggressive responding in subjects with Antisocial Personality Disorder (ASP) and matched controls. Experiment III will measure serotonin (5-HT) function using a neuroendocrine challenge and relate this measure to impulsive and aggressive behaviors in the laboratory and in the clinic. Experiment IV will determine if changes impulsivity in the laboratory parallel clinical response to treatment for cocaine dependence. The candidate's immediate career goals are to continue ongoing research on serotonin, substance abuse and impulse control. Long term career goals are to develop as a researcher in the area of the biology of impulse control and substance abuse. This will be done by defining the serotonergic receptors involved in impulse control through collaboration with experts in preclinical serotonin research, and impulsivity. Novel laboratory methods for measurement of impulsivity will be developed and validated in impulsive patient populations, and neurophysiology techniques will be used as an additional measure of 5-HT. Research Career Development Program: The research career development consists of new and expanded collaborations with scientists in the field of basic science of serotonin function, impulsivity, and laboratory measurement of human behavior.
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