Ethanol-reinforced behavior in P, NP, HAD and LAD rats: differential genetic regulation of reinforcement and motivation.

Abstract

Genetic differences exist in whether animals find ethanol or other drugs positively reinforcing. Through the use of P, NP, HAD and LAD rats, animals selectively bred for high (P, HAD) or low (NP, LAD) ethanol consumption in a two-bottle choice procedure, the present results show that multiple factors determining ethanol consumption can be identified. Ethanol-preferring P rats consumed more ethanol across all conditions involving fixed ratio or progressive schedules than did non-preferring NP, preferring HAD or non-preferring LAD rats. In both non-preferring NP and preferring HAD rats, responding decreased similarly as fixed ratio size was increased. However, under a progressive ratio schedule, NP rats responded to higher break points than did HAD rats. In LAD rats, ethanol has not consistently been shown to be a reinforcer and these rats exhibited the lowest levels of responding for ethanol across all conditions. These findings extend the conditions under which P rats have been shown to consume substantial amounts of ethanol. In addition the results illustrate genetic differences with regard to the propensity of animals to maintain ethanol-reinforced behaviors under different schedules of intermittent reinforcement, and provide further evidence that ethanol drinking in a preference paradigm is not highly predictive of whether or to what extent ethanol may come to serve as a positive reinforcer. The results suggest that the phenomenon of ethanol drinking is a composite of at least three genetically independent factors governing different aspects of ethanol-seeking behavior: (1) a permissive factor allowing animals to readily overcome the aversive sensory effects of ethanol; (2) a reinforcement factor that determines whether a substance can come to serve as a positive reinforcer; and (3) a motivational factor related to the subjects' drive state with regard to drug seeking.