PREFRONTAL CORTICAL INVOLVEMENT IN PHENCYCLIDINE-INDUCED ACTIVATION OF THE MESOLIMBIC DOPAMINE SYSTEM - BEHAVIORAL AND NEUROCHEMICAL EVIDENCE

Acute administration of phencyclidine to rats potently activates mesoc orticolimbic dopaminergic neurons. The activation of dopamine release and utilization in the prefrontal cortex and nucleus accumbens are ass ociated with profound cognitive impairment and hyperlocomotion, respec tively. This dopaminergic activation by phencyclidine is not mediated by direct effects on the cell body regions of the dopamine neurons; ho wever, phencyclidine augments dopamine release locally in the terminal fields. In the present study, the possible involvement of the prefron tal cortex in mediating activation of the mesolimbic dopamine system b y phencyclidine was examined. Ibotenic acid lesions of the prefrontal cortex attenuated the biochemical activation of the mesolimbic dopamin e neurons by PCP, and prefrontal lesions sharply blunted phencyclidine -, but not amphetamine- or novelty-, induced hyperlocomotion. In addit ion, injection of phencyclidine directly into the prefrontal cortex in creased dopamine utilization in the nucleus accumbens and induced hype rlocomotion. In summary, these studies show that phencyclidine activat es the mesolimbic pathway through a mechanism in the prefrontal cortex , possibly by disinhibiting the cortical circuit and activating cortic ofugal glutamatergic release in the ventral tegmental area.