Ethanol locomotor sensitization, but not tolerance correlates with selection for alcohol preference in high- and low-alcohol preferring mice

Rationale: Some theories have advanced a role for both locomotor sensitizat ion and tolerance in the reinforcing properties of drugs. The present studi es used selected lines of mice to assess genetic correlations among ethanol drinking, ethanol locomotor sensitization, and tolerance to the depressant effects of ethanol. Objectives: Ethanol-naive high- and low-alcohol prefer ring (HAP and LAP) selected lines of mice were tested for locomotor sensiti zation to ethanol and acquisition of acute functional tolerance to ethanol using the static dowel test. Methods: For the locomotor sensitization study , mice received four i.p. injections of one of five doses of ethanol (0-3.5 g/kg) at 48-h intervals. On the sensitization test day, 48 h after the las t drug administration day, all mice received a 2.0-g/kg ethanol injection. Other mice from the same lines were subjected to a two-injection (3.75 g/kg total), acute functional tolerance procedure assessing disruption of balan ce on a static dowel. Results: Lines differed neither in the acute locomoto r activating nor depressant effects of ethanol. Additionally, neither line' s response to the depressant effect of 3.5 g/kg ethanol changed with repeat ed injection. However, locomotor sensitization was seen in HAP but not LAP mice that had received 2.75 g/kg or 3.5 g/kg ethanol during repeated admini stration. Both HAP and LAP mice acquired equivalent acute functional tolera nce, as measured by an increase in blood ethanol concentration between the first and second recovery measures. Conclusions: Overall, these findings im ply that high ethanol consumption in mice appears to be genetically related to ethanol locomotor sensitization. Additionally, ethanol locomotor sensit ization does not appear to be related to tolerance to the depressant effect s of ethanol. These findings support a role for sensitization in high alcoh ol-seeking behavior in mice.