SUBCHRONIC PHENCYCLIDINE ADMINISTRATION INCREASES MESOLIMBIC DOPAMINERGIC SYSTEM RESPONSIVITY AND AUGMENTS STRESS-INDUCED AND PSYCHOSTIMULANT-INDUCED HYPERLOCOMOTION

Previous studies have shown that repented exposures to phencyclidine ( PCP) induces prefrontal cortical dopaminergic and cognitive deficits i n vats and monkeys, producing a possible model of schizophrenic fronta l cortical dysfunction. In the current study, the effects of subchroni c PCP exposure on forebrain dopaminergic function and behavior were fu rther explored. Prefrontal cortical dopamine utilization was reduced 3 weeks after subchronic PCP administration, and the cortical dopaminer gic deficit was mimicked by repented dizocilpine exposure. In contrast , stress-and amphetamine-induced hyperlocomotion, behavior believed to be mediated by activation of mesolimbic dopamine transmission, was en hanced after PCP exposures. Furthermore, haloperidol-induced increases in nucleus accumbens dopamine utilization were larger in magnitude in PCP-treated rats relative to control subjects. These data are the fir st to demonstrate that repeated exposures to PCP causes prefrontal cor tical dopaminergic hypoactivity and subcortical dopaminergic hyper-res ponsivity in rats, perhaps mimicking alterations in dopaminergic trans mission that underlie the behavioral pathology of schizophrenia. (C) 1 998 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.