The applicant of this award is an experience animal behavior research scientist who has studied the properties or alcohol using several behavioral paradigms. His immediate career goal is to go beyond the behavioral analysis of alcohol-related behaviors and begin a career investigating the biological mechanisms involved in determinants of risk for alcohol abuse. The training program outlined in this grant would be critically important for allowing the applicant to reach his goals by providing him with a unique set of skills for examining the anatomy and molecular physiology of neuronal pathways involved in alcohol's aversive effects and how these interact with earning to influence alcohol-seeking behavior. As a result, he will develop a scientific identity which will make him a truly competitive behavioral neuroscientist as he seeks his long-term career goal of obtaining an academic faculty position. The training environment at the University of Washington includes laboratories and faculty in the Departments of Psychology and Psychiatry. In addition to courses and technical training, a steering committee will provide the applicant with regular input and feedback throughout the project. The hypotheses outlined in the present proposal are designed to examine the neurochemical pathways that mediate the aversive properties to alcohol and alcohol-induced conditioned taste aversions (CTA). Previous research, using cFos-like immunoreactivity (cFLI) as an indication of cellular activation, has shown that the brainstem regions thought to be involved in taste aversion learning (particularly, the nucleus of the solitary tract (NTS)) are activated by alcohol and by tastes that have been paired with this drug. Proposed experiments are designed to assess the following questions about the cellular activity in the brainstem associated with alcohol administration and CTA expression: A) What are the sources of neuronal input to the brainstem which cause this cellular activation and which may mediate taste aversion learning? To examine this question, electrolytic lesions will be made in specific brain regions and subsequent effects on cFLI in the NTS and CTA acquisition/expression will be assessed. B) What is the neurochemical phenotype of cells in the brainstem that are activated by alcohol and by tastes paired with alcohol? Double-labeling-procedures with in situ hybridization histochemistry and immunohistochemistry will be used to examine this question. And C), What neurotransmitters and receptors are responsible for mediating this cellular activity in the NTS, and are these neurotransmitter systems involved with taste aversion learning? This question will be addressed by using specific receptor antagonists and receptor autoradiography. A better understanding of the neuronal mechanisms that underlie the aversive effects associated with ethanol may allow one to more accurately predict the predisposition towards alcoholism, and may be useful for the development of pharmacological treatments targeted at preventing alcohol abuse.
