Progress in this Research Component has led to successful selective breeding and maintenance of a single pair of high and low alcohol- preferring mouse lines, i.e., HAP1 and LAP1. This accomplishment and our proposal to raise by mass selection two other pairs of high and low alcohol-preferring mouse lines (i.e., HAP2/LAP2 and HAP3/LAP3) can potentially produce an important research resource for the alcohol research community at large. A control line (CAP2) will be raised contemporaneously with the HAP2/LAP2. For the next five years, efforts will be devoted to the following: 1) To continue the development of the HAP1/LAP1 lines with plans to initiate inbreeding and cryopreservation of embryos when the selective breeding reaches maximal divergence and plateaus. 2) To repeat the above experiment by raising HAP2/LAP2 (with CAP2) and HAP3/LAP3. 3) To examine in the HAP/LAP lines certain selected correlated responses: locomotor activation and sensitizing effects of ethanol; baseline anxiety and the anxiolytic effects of ethanol; the development of acute tolerance to ethanol; and hedonic effects of ethanol as measured by conditioned taste aversion, operant oral self- administration and conditioned place preference. 4) To evaluate whether some of the putative quantitative trait loci reported by others can be confirmed in the HAP/LAP lines. 5) To measure in alcohol-naive HAP/LAP mice the steady state levels of serotonin (5-HT), dopamine, and met- enkephalin. 6) To evaluate the hypothesis forwarded by Badawy, i.e., alcohol preference in mice is due to higher serum corticosterone levels and thus higher hepatic tryptophan (Trp) pyrrolase activities and decreased brain contents of Trp and 5-HT. Most of the methods are already established in our Alcohol Research Center or will be carried out by Dr. Nicholas Grahame who has recently joined the Center.
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