INVOLVEMENT OF GAMMA-AMINOBUTYRIC-ACID NEUROTRANSMISSION IN PHENCYCLIDINE-INDUCED DOPAMINE RELEASE IN THE MEDIAL PREFRONTAL CORTEX

The present study was designed to examine the possible involvement of gamma-aminobutyric acid (GABA) neurotransmission in the mechanism of p hencyclidine (1-(1-phenylcyclohexyl)piperidine; PCP)-induced dopamine release in the medial prefrontal cortex, using in vivo microdialysis i n awake, freely moving rats. Local perfusion via the dialysis probe in to the medial prefrontal cortex with PCP (100 and 500 mu M) and dizoci lpine dihydroxy-5-H-dibenzo(a,d)cyclo-heptan-5,10-imine; MK-801, 10 an d 50 mu M), a selective non-competitive NMDA receptor antagonist, was found to increase extracellular dopamine levels. Go-perfusion with NMD A(I mM) or the GABA(A) receptor agonist muscimol (50 mu M) attenuated the effects of PCP (500 mu M) and MK-801 (50 mu M) On extracellular do pamine levels. The dopamine reuptake inhibitor nomifensine (50 mu M) a lso produced an increase in extracellular dopamine levels in the media l prefrontal cortex, but this effect was not affected by co-perfusion with muscimol (50 mu M) On the other hand, local perfusion with PCP (1 00 and 500 mu M) and MK-801 (10 and 50 mu M), but not nomifensine (50 mu M), reduced extracellular GABA levels in the medial prefrontal cort ex. Go-perfusion with NMDA (1 mM) reduced the effects of PCP (500 mu M ) and MK-801 (50 mu M) on extracellular GABA levels. These results sug gest that PCP may facilitate dopamine release in the medial prefrontal cortex, at least in part, by the inhibition of GABA release via the a ntagonism of NMDA receptors. (C) 1998 Elsevier Science B.V.