Object retrieval/detour deficits in monkeys produced by prior subchronic phencyclidine administration: Evidence for cognitive impulsivity

Background: Impulsivity associated with frontal cortical dysfunction appear s to be a direct consequence of chronic consumption of drugs of abuse, thou gh few investigations in animals have attempted to directly address this is sue. In this study the effects of repeated, intermittent administration of a psychotomimetic drug of abuse, phencyclidine, on the acquisition and perf ormance of a task sensitive to corticostriatal function was examined in non human primates. Methods: Monkeys were repeatedly exposed to phencyclidine (0.3 mg/kg) twice daily for 14 days. Acquisition and performance on an object-retrieval deto ur task was subsequently examined for up to 28 days after drug withdrawal. Results: Animals treated with phencyclidine exhibited impaired acquisition of the task. The performance of trials requiring inhibitory control (as opp osed to solely sensory-guided responding) was specifically impaired by prio r phencyclidine administration. impairments were found to be due to increas ed perseveration and barrier reaching. As is the case after frontal cortex ablation, the behavioral deficits were particularly evident during acquisit ion and appeared to be alleviated by prolonged training. Conclusions: The current data demonstrate that subchronic administration of phencyclidine can produce deficits in inhibitory response control that are manifest as impulsivity (increased control of behavior by unconditioned, a ppetitive stimuli). These data suggest that long-term phencyclidine exposur e induces frontostriatal-like cognitive impairments and may represent a pot ential (drug induced) model for the study of prefrontal cortical cognitive and dopaminergic dysfunction. (C) 2000 Society of Biological Psychiatry.