The rapid onset of ethanol tolerance in Wistar rats following intensive practice on the moving-belt task.

The influence of intensive practice on the onset of ethanol tolerance was studied in the Wistar rat. The moving-belt task was used to provide a graded measure of ethanol-induced ataxia by recording the percentage of time the animal stepped off a moving belt onto a shock-grid floor during a 100-sec trial (% TOB). Naive rats were sensitive to doses between 1.9 g/kg (< 1% TOB) and 3.1 g/kg (100% TOB); the ED50 was 2.5 g/kg. To study acute tolerance, rats were maintained at a constant blood ethanol concentration of 2.8–3.2 mg/ml for 6 to 8 hr. Rats which were tested hourly during this time developed tolerance, with error times decreasing from 90 to 12% TOB. Rats which remained in their cages with no opportunity to practice did not show improvement when tested at 6 to 8 hr, although they had received similar ethanol exposure. To study chronic tolerance, the dose-response curve was monitored on odd-numbered days for 1 week. On Days 2, 4, and 6, rats received intensive practice under the influence of ethanol for five hr. Rapid tolerance developed, indicated by an increase in the ED50 from 2.5 to 3.1 g/kg. The greatest increment occurred following the first intensive practice day. In contrast, rats given minimal practice over 4 days showed no detectable tolerance. These experiments demonstrate a rate of tolerance acquisition more rapid than previously reported, and indicate that practice while under the influence of ethanol plays a major role in the onset of tolerance measured on a behavioral task.