Responses to ethanol in C57BL/6 versus C57BL/6 × 129 hybrid mice

Although genetic background alters responses to ethanol, there has not yet been a methodical quantification of differences in ethanol-related behaviors between inbred and hybrid mice commonly used in gene-targeting studies. Here, we compared C57BL/6NTac × 129S6/SvEvTac F1 hybrid mice (B6129S6) with C57BL/6NTac inbred mice (B6NT), and C57BL/6J × 129X1/SvJ (B6129X1) and C57BL/6J × 129S4/SvJae F1 hybrids (B6129S4) with C57BL/6J mice (B6J), in five commonly used tests: continuous access two-bottle choice drinking, intermittent limited-access binge drinking, ethanol clearance, ethanol-induced loss of the righting reflex, and conditioned place preference (CPP) for ethanol. We found that inbred B6J and B6NT mice showed greater ethanol preference and consumption than their respective hybrids when ethanol was continuously available. Within the intermittent limited-access drinking procedure, though all lines showed similar intake over eight drinking sessions, the average of all sessions showed that B6NT mice drank significantly more ethanol than B6129S6 mice. In addition, B6J mice consumed more ethanol than B6129X1 mice, although they drank less than B6129S4 mice. No differences in ethanol LORR duration were observed between inbred and hybrid mice. Although ethanol clearance was similar among B6J mice and their respective hybrids, B6NT mice cleared ethanol more rapidly than B6129S6 mice. All lines developed CPP for ethanol. Our findings indicate that it may not be necessary to backcross hybrids to an inbred B6 background to study many ethanol-related behaviors in gene-targeted mice.