Impairments of reversal learning and response perseveration after repeated, intermittent cocaine administrations to monkeys.

The current experiments examined the effects of acute or repeated, intermittent administrations of cocaine on the acquisition and reversal of object discriminations by Vervet monkeys in order to test the hypothesis that cocaine treatment affects performance of tasks that depend upon the functions of the orbitofrontal cortex and amygdala. An acute dose of cocaine (1 mg/kg; 20 min prior to testing) impaired reversal of a previously learned object discrimination but had no effect on acquisition of a novel one. Specific impairments of reversal learning were also observed in monkeys 9 and 30 days after repeated administrations of cocaine (2 or 4 mg/kg, once daily for 14 days) that were perseverative in nature, indicating persistent behavioral consequences of repetitive dosing. The results indicate that repeated cocaine administrations produce enduring impairments of object discrimination learning when the inhibition of a previously conditioned response is required. These findings suggest that long-term cocaine administration may disrupt orbitofrontal efferents to the striatum, resulting in impaired inhibition of established conditioned responses.