Development and loss of tolerance to the effects of ethanol on DRL performance of rats.

Six male Sprague-Dawley rats were trained on a DRL-20 operant schedule for food presentation. When stable performance was established, they were exposed to an escalating regimen of daily ethanol administration (1.125-3.75 g/kg, IP). This dosing regimen continued until the maximally tolerable dose for each subject was reached. Tolerance loss then was monitored for approximately 6 months by periodic ethanol challenge doses (1.5 g/kg). Dose-effect curves (DECs) were obtained prior to (DEC-1), immediately after (DEC-2), and 6 months following termination of (DEC-3) the ethanol exposure. Rate-increasing effects (DEC-1) were noted at low doses (0.75 and 1.125 g/kg), with a higher dose (2.25 g/kg) resulting in a decreased rate of responding. Tolerance, following chronic ethanol exposure, developed to both the rate-increasing and rate-decreasing effects of ethanol (DEC-2). While some tolerance was lost within the 6 months following the daily ethanol exposure (DEC-3), a significant degree of tolerance was still indicated by most of the response measures. This duration of tolerance was considerably longer than that generally reported, and is probably attributable to persistent learned compensatory behavior and/or intermittent ethanol challenge tests.