This proposal is a request for an ADAMHA RSDA (Level II) to assist in the growth and development of the applicant's research career and to expand his potential for making important contributions to the field of alcoholism. The proposed research is interdisciplinary, utilizing genetic manipulation and principles of quantitative genetics together with neuropharmacology and neurochemistry to study processes underlying vulnerability to alcohol abuse and alcoholism. The research will use lines of mice (LS/Ibg and SS/Ibg) genetically selected for differences in central nervous system (CNS) sensitivity to ethanol and LSXSS recombinant inbred (RI) strains derived f rom the LS and SS mice. Studies of genetic correlations among acute responses to alcohol, such as loss of righting response, motor activities and hypothermia, and neurochemical actions of alcohol, are designed to determine the extent to which various actions of ethanol are related and to examine relevant hypotheses regarding the biochemical bases for CNS actions of ethanol. Biochemical studies will include a thorough characterization of brain neurotensin systems, including levels, release, metabolism, receptors, and receptor-coupled processes and the effects of ethanol on these processes, in LSXSS RI strains and inbred strains of SS (ISS) and LS (ILS) derived from the SS and LS selectively bred lines of mice.
