ACUTE TOLERANCE TO THE ATAXIC EFFECTS OF ETHANOL IN SHORT-SLEEP (SS) AND LONG-SLEEP (LS) MICE

The objective of this series of studies was to examine the relationshi p between alcohol sensitivity and the development of very rapid acute tolerance to alcohol in mice. In order to measure acute tolerance to a lcohol, a behavioral test was developed using a rotorod. In the first study, mice selectively bred for resistance (short sleep, SS) or sensi tivity (long sleep, LS) to the acute hypnotic effects of ethanol were used, as well as mice from the base population (heterogenous stock, I- IS). Mice were trained to run on the rotorod at a speed of 14 rpm to a criterion of 200 s, in four daily training sessions. On the test day, baseline measurements of rotorod performance were taken and mice were injected IP with alcohol in doses from 0 to 2.5 g/kg. Animals were te sted at 1-min intervals for the first 5 min following injection, then at 5-min intervals for a total of 30 min. The results demonstrated tha t SS and HS mice developed tolerance within 10 min following the alcoh ol injections. LS mice did develop some acute tolerance, but at a much slower rate than the SS or I-IS mice. In the second study, the effect s of intoxicated practice on the rates of acute tolerance development were examined in the SS, I-IS and LS mice at a dose of 2.0 g/kg alcoho l. A total of ten groups of each strain were given a different number of practice trials (ranging from one to ten) on the rotorod prior to a final test session at 30 min post-injection. The results provide evid ence that SS and HS mice are capable of developing acute tolerance ind ependent of practice. That is, the group of animals injected at 0 time and tested ten times up to 30 min were no better at the 30-min time p oint than the group injected at 0 time and tested only once at 30 min. On the other hand, the LS mice showed a modest practice effect, devel oping additional tolerance to the ataxic effects of alcohol with incre asing intoxicated practice. Overall, these studies demonstrated that m ice can develop acute tolerance within minutes following alcohol expos ure, and that this ability is correlated with the initial sensitivity to alcohol.