Effects of sex on ethanol conditioned place preference, activity and variability in C57BL/6J and DBA/2J mice

Previous studies of ethanol drinking in rodents have shown greater intake in females than in males, but the reasons behind this difference are unknown. To address one possible interpretation of the drinking difference, these studies tested the hypothesis that female and male mice differ in sensitivity to the rewarding effects of ethanol using the conditioned place preference (CPP) procedure. To increase the generalizability of the results, sex differences were examined in two inbred mouse strains known to differ in their sensitivity to ethanol reward: C57BL/6J (B6) and DBA/2J (D2). Mice were conditioned in an unbiased CPP procedure using either 1 or 2 g/kg ethanol. To detect possible differences in learning rate, they were tested once at the midpoint of conditioning and again after conditioning ended. As expected, CPP was stronger with 2 g/kg than with 1 g/kg, and D2 mice generally showed stronger CPP than B6 mice. However, there were no sex differences in the rate of CPP acquisition or in CPP magnitude, suggesting no sex difference in ethanol reward sensitivity as indexed by CPP. Nevertheless, there were sex differences in locomotor activity. B6 females were generally more active than B6 males during CPP acquisition whereas D2 females were slightly less active than D2 males during both CPP acquisition and preference testing. Unexpectedly, female mice showed more variability than males in the behavioral measures recorded in these studies, encouraging greater attention to variability in the design, analysis and interpretation of future studies of sex differences in mice.