Ethanol self-administration is genetically independent of locomotor stimulation in fast and slow mice

One substance abuse hypothesis proposes that rewarding effects of drugs are causally related to their psychostimulant effects. We examined this hypothesis by comparing operant self-administration of ethanol in mice selectively bred for either high (Fast) or low (Slow) locomotor stimulation response to ethanol. Mice were trained to lever press for ethanol using postprandial induction and were then tested over a range of conditions to determine the degree of self-administration. There were no significant differences between Fast and Slow mice in either the amount of work produced to obtain ethanol or the amount of ethanol consumed. In general, none of the groups of mice showed robust ethanol-reinforced behavior. This is in contrast with C57BL/6J mice tested concurrently, which showed substantial ethanol-reinforced behavior. Further analysis revealed individual differences in responding within each of the selected lines. However, there was no systematic pattern within or between groups for these individual differences, suggesting that the genes mediating ethanol-reinforced behavior are segregating in a manner independent from genes mediating the locomotor stimulant response to ethanol, and thus, the mechanistic processes mediating reinforcement from ethanol are distinct from those that influence the psychomotor stimulant response to this drug.