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

BACKGROUND Impulsivity associated with frontal cortical dysfunction appears to be a direct consequence of chronic consumption of drugs of abuse, though few investigations in animals have attempted to directly address this issue. In this study the effects of repeated, intermittent administration of a psychotomimetic drug of abuse, phencyclidine, on the acquisition and performance of a task sensitive to corticostriatal function was examined in nonhuman primates. METHODS Monkeys were repeatedly exposed to phencyclidine (0.3 mg/kg) twice daily for 14 days. Acquisition and performance on an object-retrieval detour 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 opposed to solely sensory-guided responding) was specifically impaired by prior phencyclidine administration. Impairments were found to be due to increased perseveration and barrier reaching. As is the case after frontal cortex ablation, the behavioral deficits were particularly evident during acquisition 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, appetitive stimuli). These data suggest that long-term phencyclidine exposure induces frontostriatal-like cognitive impairments and may represent a potential (drug induced) model for the study of prefrontal cortical cognitive and dopaminergic dysfunction.