The proposed plan is to carry out ongoing research based on a previously funded RO-1 grant entitled """"""""Ethanol-corticosterone-GABAergic interactions in LS and SS mice"""""""", and to broaden technical expertise in the area of molecular genetics. Participation in the ongoing research will be increased by a reduction of Dr. Wehner's current teaching load. Her immediate goal of understanding the role of stress in ethanol sensitivity will be pursued by engaging in current studies of stress/ethanol interactions regulating behavioral responses and examining the actions of steroids and ethanol at the GABA/Benzodiazepine receptor. The research plan includes examining the role of corticosterone in regulation of CNS sensitivity to ethanol using several behavioral measures. Long-sleep and short-sleep mice will be used because they differ in ethanol-induced corticosterone release and GABAergic receptors. Corticosterone levels will be manipulated by adrenalectomy, acute corticosterone treatments, and inhibition of corticosterone synthesis. The long-term goals of the research are to understand genetic regulation of ethanol sensitivity and changes occurring as a consequence of chronic stress and ethanol treatment. These goals will be pursued by acquiring training in molecular genetic techniques. These include quantitative trait loci mapping techniques, polymerase chain reaction techniques, and data analyses pertaining to mapping. These technologies are available in Dr. Thomas Johnson's laboratory at the University of Colorado. Thus, training in molecular genetics can be accomplished with- out leaving the candidate's home institution. Studies designed to understand the genetic regulation of differences in the above parameters in LS and SS mice will be pursued using recombinant inbred strains. Techniques for quantitative trait loci mapping will be applied as the technique are acquired by the candidate.
