THE EFFECT OF PHENCYCLIDINE ON THE BASAL AND HIGH POTASSIUM-EVOKED EXTRACELLULAR GABA LEVELS IN THE STRIATUM OF FREELY-MOVING RATS - AN IN-VIVO MICRODIALYSIS STUDY

The effect of phencyclidine (PCP) on the gamma-aminobutyric acid-ergic (GABAergic) transmission in the striatum of freely-moving rats was in vestigated using an in vivo microdialysis. The high potassium (100 mM) increased the extracellular GABA level to 4000% of the basal level. A lthough the basal GABA level in the striatal dialysate did not show ei ther calcium dependency or tetrodotoxin (TTX) sensitivity, the high po tassium evoked GABA level was reduced by 82% under calcium-free condit ions (with 12.5 mM magnesium) and by 54% in the presence of 10 mu M TT X. The systemic administration of PCP (7.5 mg/kg) or the local perfusi on of PCP (100 mu M and 1 mM) significantly inhibited the high potassi um evoked GABA release in the rat striatum. The local perfusion of MK- 801 (10 mu M and 100 mu M), a more potent and selective N-methyl-D-asp artate (NMDA) receptor antagonist, also inhibited the high potassium e voked striatal GABA release. These drugs did not show any significant effect on the basal extracellular GABA level. NMDA (1 mM) either partl y or completely blocked the effect of PCP (1 mM) or MK-801 (100 mu M) on the high pottasium evoked striatal GABA release. On the other hand, nomifensine (100 mu M), a dopamine uptake blocker, did not show any e ffect on the high potassium evoked GABA release. These results suggest that PCP inhibited the striatal GABAergic neuronal transmission throu gh its antagonism of the NMDA receptor.