Development of functional tolerance to ethanol in rhesus monkeys (Macaca mulatta)

Four rhesus monkeys were extensively trained until performance reached asymptote on a two-choice discrimination-reversal task. Doses of ethanol (3 g/kg) or placebo (aqueous lactose solutions isocaloric to 3 g/kg of ethanol) were then administered by gavage 90 min prior to testing. Following an initial decrement when ethanol was first administered, performance gradually returned on subsequent days to levels which were equivalent to those found under placebo conditions despite continued drug administration. Ethanol treatment affected accuracy of responding during both the acquisition and reversal phases of the task as well as the quantity of behavior emitted by the animals. Changes in performance levels were independent of fluctuations in blood ethanol concentrations. Functional tolerance developed within approximately 18 days as indicated by the recovery of performance on the discrimination-reversal task. Furthermore, this tolerance was retained during a 24 day period during which no ethanol was administered.