SUBCHRONIC PHENCYCLIDINE ADMINISTRATION REDUCES MESOPREFRONTAL DOPAMINE UTILIZATION AND IMPAIRS PREFRONTAL CORTICAL-DEPENDENT COGNITION IN THE RAT

Repeated ingestion of phencyclidine by humans induces enduring schizop hrenic symptomatology, particularly cognitive dysfunction. In the pres ently described series of experiments, the neurochemical and cognitive consequences of subchronic phencyclidine administration in the rats w ere explored. Repeated phencyclidine exposure led to a selective reduc tion in basal and stress-evoked dopamine utilization in the prefrontal cortex. In addition, rats previously subchronically-treated with phen cyclidine were impaired on performance of a spatial working memory tas k in a delay-dependent manner. Importantly, these dopaminergic and cog nitive deficits were observed after withdrawal from phencyclidine, and as such, the neurochemical and behavioral effects were due to drug-in duced neurobiological changes rather than direct drug effects. These b iochemical and behavioral data show that repeated phencyclidine admini stration induces prefrontal cortical cognitive deficits in rats, as in humans, and offer a biochemical perspective of the neural substrate u nderlying this cognitive impairment: inhibition of mesocortical dopami ne neurons. Thus, these data may have relevance to psychiatric disorde rs involving prefrontal cortical dopaminergic hypoactivity and cogniti ve dysfunction, as has been hypothesized in schizophrenia. (C) 1997 Am erican College of Neuropsychopharmacology. Published by Elsevier Scien ce Inc.