This proposal is a request for an ADAMHA Research Scientist Development Award which would enable the applicant to continue and significantly enhance a career in alcohol research. At present, the applicant is a co-investigator of an NIAAA-supported Alcohol Research Center and Associate Professor in the School of Pharmacy at the University of Colorado. Currently, faculty and administrative commitments allow him to devote 25-30% of his time to research. This award would enable him to devote essentially full-time to research on pharmacogenetics of the neurotoxicity of alcohol. The proposed research includes the use of genetic stocks of mice (MEW/Ibg, SEW/Ibg, DBA, and C57BL) which display genetic diversity in severity of withdrawal following chronic alcohol administration. The broad objective of the proposed research is to identify brain mitochondrial dysfunctions induced by chronic alcohol ingestion. Brain mitochondrial properties proposed to be characterized include bioenergetics, membrane fluidity, and CA++ translocation. The studies will characterize chronic alcohol- induced changes in brain mitochondria biogenic amine/aldehyde metabolism and thiol homestasis in mitochondria and synaptosomes. The research is interdisciplinary in that behavioral correlates (avoidance behavior) of the biochemical and neurochemical alterations will be identified and characterized. Another interdisciplinary feature of the proposed studies will be additional quantitative and biochemical genetic analyses of the SEW/Ibg and MEW/Ibg selected lines of mice.
