Characterization of the Phenomenon of rapid tolerance to ethanol.

Motor impairment (tilt-plane) and hypothermia tests were used to further characterize the phenomenon of rapid tolerance to ethanol. Five experiments were carried out to clarify the relationship between rapid and chronic tolerance. The first experiment demonstrated that the extent of tolerance on day 2 produced by the single dose of 4 g/kg alcohol on day 1 was similar to that resulting from two divided doses, administered 2 h apart. In the second experiment, a linear relationship between treatment dose and rapid tolerance development was demonstrated in that higher day 1 treatment doses resulted in greater rapid tolerance development. In the third, a parallel dose-response relationship, similar to that known for chronic tolerance, was observed for rapid tolerance. In the fourth experiment, we compared the development of rapid tolerance under three different conditions: (a) in groups of rats that were not subjected to testing at all (no testing); on day 1, (b) in groups of rats that were not tested on the apparatus but handled at all test times on day 1 (dummy testing); and (c) in groups of rats that were tested at all test times on day 1 (testing or intoxicated group). No testing on day 1 failed to produce rapid tolerance to ethanol whereas testing and dummy testing of animals on day 1 after pretreatment with ethanol-produced rapid tolerance to ethanol on day 2. In the last experiment, immediate posttrial administration of ketamine was found not to block rapid tolerance development. These findings provide additional support for similarities between the mechanisms of rapid and chronic tolerance.