Effects of the cannabinoid ligand SR 141716A alone or in combination with Δ9-tetrahydrocannabinol or scopolamine on learning in squirrel monkeys

To investigate the effects of the cannabinoids on learning and on scopolamine-induced disruptions in learning, Delta(9)-tetrahydrocannabinol (Delta(9)-THC), SR 141716A (an antagonist at CB1 receptors) and scopolamine were administered to squirrel monkeys responding in a repeated-acquisition task In this task, monkeys acquired a different three-response sequence each session and responding was maintained by food presentation under a second-order fixed-ratio 5 schedule. When either Delta(9)-THC (0.1-0.56 mg/kg, i.m.) or SR 141716A (1-10 mg/kg, i.m.) was administered alone, 60 and 75 min before the session, respectively, both cannabinoid ligands dose-dependently decreased the overall rate of responding and increased the overall percentage of errors. However, at a dose that had little or no effect alone (i.e. 1 mg/kg), SR 141716A antagonized the disruptive effects of Delta(9)-THC (0.18-1.8 mg/kg) on acquisition, shifting the dose-effect curves for rate of responding and percentage of errors at least 1/2 log unit to the right. Finally, when either Delta(9)-THC (0.001-1 mg/kg) or SR 141716A (0.32-10 mg/kg) was administered with scopolamine (0.01 or 0.032 mg/kg, 15 min before the session), greater rate-decreasing and error-increasing effects were obtained than with scopolamine alone. These results suggest that while low doses of SR 141716A can antagonize the effects of Delta(9)-THC in squirrel monkeys, high doses can also disrupt acquisition when administered alone and potentiate the disruptive effects of scopolamine on acquisition. (C) 2000 Lippincott Williams & Wilkins.