Operant rate depressant effects of ethanol in mice selectively bred for differential neurosensitivity to ethanol

Few studies have investigated genetic differences in the effects of ethanol on operant schedule-controlled behaviors. The use of genetically defined populations in sensitive measures of complex behavior can help determine genetically covarying responses to ethanol as well as environmental contexts important for demonstrating genetic differences. The purpose of the present study was to investigate the rate depressant effects of ethanol on two lines of mice selectively bred for increased, LS/Ibg (LS), and decreased, SS/Ibg (SS), sensitivity to the acute narcotic effects of ethanol. Ethanol dose-dependently decreased high rates of behavior maintained by fixed ratio responding for water in both the LS and SS mice. Interestingly, the LS and SS mice did not differ in the rate depressant effects of ethanol under these conditions despite the sensitivity of this measure to the CNS effects of drugs and the very large differences between these lines in sensitivity to numerous other ethanol-related effects. While the SS mice were slightly less sensitive, and LS mice tended to show a low dose rate increasing effect, none of the differences were significant as ED50 values for rate depression differed by only 2.5 percent. The results of this experiment demonstrate that sensitivity to the effects of ethanol on fixed ratio responding for water is not genetically related to the acute narcotic effects of ethanol. In addition, the findings show that previously reported differences in operant ethanol self-administration between these two lines of mice are not due to differential sensitivity to the direct effects of ethanol on reinforced behavior.