ACUTE BEHAVIORAL-EFFECTS OF MK-801 IN RHESUS-MONKEYS - ASSESSMENT USING AN OPERANT TEST BATTERY

The acute effects of MK-801, a selective, noncompetitive NMDA receptor antagonist, were assessed using an operant test battery (OTB) of comp lex food-reinforced tasks that are thought to depend upon relatively s pecific brain functions such as motivation to work for food (progressi ve ratio, PR), learning (incremental repeated acquisition, IRA), color and position discrimination (conditioned position responding, CPR), t ime estimation (temporal response differentiation, TRD), and short-ter m memory and attention (delayed matching-to-sample, DMTS). Endpoints i ncluded response rates (RR), accuracies (ACC), and percent task comple ted (PTC). MK-801 (0.003-0.075 mg/kg, IV), given 15 min pretesting, pr oduced significant dose-dependent decreases in measures of IRA and TRD performance at doses greater than or equal to 0.03 mg/kg. In both tas ks, MK-801 produced significant decreases in accuracy at doses lower t han those required to affect response rate. MK-801 also produced stati stically significant decreases in PR, CPR, and DMTS measures, but only at higher doses (greater than or equal to 0.056 mg/kg) that caused si gnificant decreases in both response rates and accuracies. These resul ts indicate that, in monkeys, performance of operant tasks designed to model learning and time estimation is more sensitive to the disruptiv e effects of MK-801 than performance of tasks that model motivation, c olor, and position discrimination, and short-term memory and attention .