Genetic differences in tolerance and sensitization to the sedative/hypnotic effects of alcohol.

Initial sensitivity to alcohol and the development of alcohol tolerance were examined in rats of the selectively bred alcohol-preferring (P) and -nonpreferring (NP) lines. All rats received two alcohol injections (3.0 g/kg b.wt., IP) separated by either 1 or 2 days. P rats were less sensitive to the behaviorally impairing effects of alcohol than were NP rats, as evidenced by a longer latency to lose righting reflex (RR) and a shorter time to recover RR following an initial alcohol injection. When 1 day separated the two alcohol injections, P rats recovered the RR more rapidly following a second injection compared to the first, indicating that the P rats developed tolerance to the sedative/hypnotic effects of alcohol. In contrast, the NP rats recovered the RR more slowly following the second injection compared to the first, indicating that the NP rats developed sensitization to alcohol. Tolerance in the P line and sensitization in the NP line disappeared when 2 days separated the two alcohol injections. Line differences in initial sensitivity and tolerance/sensitization to the behaviorally impairing effects of alcohol may contribute to the differences in alcohol consumption observed in the P and NP lines.