Differential effects of chronic alcohol on GABA(A)‐ and NMDA‐receptor mediated disruptions in learning in rhesus monkeys

Abstract

To examine the chronic effects of alcohol on learning, 2 groups (−ETOH, +ETOH) of young male rhesus monkeys trained to respond under a task with acquisition and performance components received ethanol 4 consecutive days per week for 12 months via an intragastric catheter. Cumulative dose-effect curves for both flunitrazepam (0.056–0.56 mg/kg, i.m.) and ketamine (1.8–10 mg/kg, i.m.) were determined in each group before and after chronic ethanol. During the three days of the week when ethanol was not administered, little or no disruptions were observed in either response rate or the percentage of errors (accuracy) in either component compared to control subjects. During the two days of testing during ethanol administration, modest disruptions in response rate and percent errors occurred in the acquisition components; the disruptions were larger on the initial day than on the second day. When cumulative doses of flunitrazepam and ketamine were administered in the absence of ethanol, dose-dependent decreases in response rate and accuracy occurred in both components. Over time, however, chronic ethanol administration shifted the dose-effect curves for flunitrazepam to the right, whereas the curves for ketamine were unchanged. These results indicate that chronic alcohol administration may produce larger changes in GABA(A) receptor function than NMDA receptor function in monkeys. Supported by USPHS AA09803.