This proposal describes a quantitative trait loci (QTL) search for rat genes mediating ethanol preference. We recently completed a QTL study of morphine preference (during a two-bottle choice experiment) in inbred mice. As an extension of this paradigm, we propose a QTL study of two outbred rat lines (ALKO Alcohol and ALKO Non-Alcohol) known to differ markedly in ethanol intake during a two-bottle choice experiment. The F2 generation from an intercross of these two lines will be studied for ethanol intake in a two-bottle choice experiment. Preliminary data suggest that sufficient informative DNA markers exist to make genomic scanning feasible. Genotypes across the rat genome for the F1 and F2 generations will be established, and composite interval mapping regression analyses will be conducted to determine the location of genes which mediate the large differences in ethanol intake between these two rat lines. The loci identified through this research may yield important genetic clues regarding human vulnerability to alcoholism.
