Regulation of operant ethanol-reinforced behavior is genetically independent of regulation of withdrawal severity in WSP and WSR mice

Abstract

Selectively bred withdrawal seizure prone (WSP1 and WSP2) and withdrawal seizure resistant (WSR1 and WSR2) mice were used to test the extent to which severity of ethanol withdrawal response is predictive of the reinforcing effects of ethanol. Mice were systematically introduced to ethanol under a fixed ratio 1 (FR 1) schedule using adjunctive drinking methods. There were no significant differences in ethanol consumption between the lines during training. Subsequently, responding for ethanol concentrations of 8%, 0% (vehicle control), and 8% retest under a FR 1 schedule in the absence of food induction was measured. Group data showed that ethanol did not serve as a reinforcer in the test phase within any of the four lines, and there were no significant line differences in rate of responding, intake, or blood ethanol concentrations (BEC). Mice were next tested for responding for ethanol under a FR 4 schedule. Again, ethanol did not serve as a reinforcer for any of the four groups, and there were no significant differences between the lines. However, further analysis showed that there were individual differences in responding within each group, some animals were apparently reinforced by ethanol, while others showed no reinforcement and some appeared to avoid ethanol. There was no systematic pattern within or between groups for these individual differences in responding. Thus, both the group results as well as the behavior patterns of individual animals are consistent with the conclusion that genes regulating rewarding effects of ethanol appear to be segregating randomly across groups and are independent of genes mediating ethanol withdrawal severity. These findings indicate a lack of association between propensity to develop physical dependence on ethanol and propensity to find this drug reinforcing.