This research component is founded on the general notion that genetic difference in sensitivity to ethanol's reinforcing efficacy are importantly related to the development of maladaptive patterns of ethanol use. However, the gene or genes responsible for differential ethanol-mediated responding have not been determined. The initial objective of this 5-year project is to characterize quantitative trait loci (QTLs) associated with ethanol-reinforced responding. Ethanol reinforcement in a continuous access operant procedure will be determined in BXD recombinant inbred mice. Further, the genetic relationship between ethanol, food and water intake will be examined as well as genetic differences in the pattern (episodic and food related) of ethanol intake. For example, our preliminary studies suggest the BXD parental strains (C57B1/6J, DBA/2J) differ in the rate of operant ethanol responding, episodic pattern of ethanol responding and in the type (prandial/nonprandial) of ethanol responding. Establishment of a BXD RI data set consisting of reinforcement related behaviors will enable the determination of chromosomal map locations (QTL) associated with a number of phenotypes (e.g. ethanol reinforcement, food reinforcement, drinking type). Further, comparisons of QTLs associated with other ethanol response (e.g. place preference, locomotor activation, taste aversion) will allow for the precise determination of genetic overlap with ethanol reinforcement. The second objective of this project is to characterize operant ethanol reinforcement in selectively bred FAST/SLOW, HOT/COLD and WSP/WSR mice. These studies will determine genetic correlations between ethanol reinforcement and the selection phenotypes and test hypotheses related to putative mechanisms of ethanol reinforcement (e.g. locomotor stimulation, hypothermia). Overall, the present project will provide important new information on the genetic mechanisms underlying ethanol's reinforcing effects and contribute to the growing genetic data set collected by center investigators and others. Further, these studies will provide the background information necessary for the eventual identification of genes responsible for excessive ethanol-seeking behavior.
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