Genetic tools in the study of drug self-administration.

Recent studies have shown that large genetic differences exist in the extent to which orally delivered ethanol will come to serve as a positive reinforcer under operantly defined conditions. In addition, these studies suggest that a significant correlation exists between results from two-bottle choice studies of ethanol drinking and operant self-administration studies of ethanol functioning as a reinforcer. The present paper reports further genetic influences on ethanol self-administration which were found using Long Sleep and Short Sleep mice, bred selectively for high and low duration of loss of the righting reflex in responses to ethanol, respectively. It was possible to establish ethanol as a reinforcer in Long Sleep mice but not in Short Sleep mice. These results indicate that neurosensitivity to ethanol may determine the absolute amount of ethanol consumption but is not highly related to the ability of ethanol to serve as a positive reinforcer. In addition, this paper presents genetic correlations which indicate that (a) ethanol preference and self-administration are highly correlated across genotype; (b) sensitivity to ethanol and self-administration of this drug are not highly genetically correlated; (c) ethanol is not self-administered in operant studies solely for its caloric value; and (d) there exist important genetic determinants of drug reinforced behavior.