This issue should be carefully considered when trying to parse

out differences in ethanol drinking between mice of different genetic backgrounds. Since differences in ethanol metabolism can alter blood ethanol levels, we examined ethanol clearance. The only major difference in clearance we observed was between B6NT and B6129S6 mice at 120 and 180 min postethanol injection, when the hybrids showed slower clearance. The basis for the difference in clearance between these strains is not clear but might relate to strain differences in enzymes that metabolize ethanol and acetaldehyde. B6 mice and certain substrains of 129 mice have different Inhibitors,research,lifescience,medical alleles of the gastric isozyme of ethanol dehydrogenase, Inhibitors,research,lifescience,medical Adh-3, but the same alleles of the liver isozyme Adh-1 (Holmes et al. 1982). However, this cannot account for the differences in clearance observed here, since ethanol was administered intraperitoneally

in this experiment. To determine if the behavioral response to a hypnotic dose of ethanol was different among the strains, we measured the duration of the LORR. Paralleling the clearance results, the B6129S6 mice displayed a trend toward a longer LORR duration than their B6NT counterparts, Inhibitors,research,lifescience,medical although this trend was not statistically Inhibitors,research,lifescience,medical significant. Delayed clearance in B6129S6 mice might have contributed to this trend, but recovery from the LORR occurred much earlier (20–30 min) than when the strains showed significant differences in clearance (2–3 h). The development of acute tolerance is a major pharmacodynamic factor that determines recovery from the ethanol-induced LORR (Wallace et al. 2007). Although our clearance and LORR experiments Inhibitors,research,lifescience,medical are not entirely comparable

since we administered different doses of ethanol (4.0 g/kg for clearance and 3.6 g/kg for LORR), our inability to detect differences in LORR duration might be due to more and rapid development of acute tolerance to ethanol in B6129S6 mice compared with B6NT mice, which could dampen the delaying effect of slower ethanol clearance on LORR recovery. We noted a rather large difference in initial blood alcohol levels at 30 min post-ethanol injection between Taconic and Jackson B6 mice tested in different sessions. To Capmatinib cost investigate this phenomenon more closely, we compared clearance between B6NT and B6J mice tested together in the same session, and found no difference in either initial blood alcohol levels or clearance rates (Supplemental Fig. 1). We thus concluded that the differences seen between sessions may have been due to variations in environment and timing. In a final series of experiments, we tested for CPP to ethanol.