Intra-striatal phencyclidine inhibits N-methyl-D-aspartic acid-stimulated increase in glutamate levels of freely moving rats.

1. The authors investigated the effect of local phencyclidine (phenylcyclohexylpiperidine, PCP) on extracellular levels of glutamate and gamma-amino butyric acid (GABA) in rat striatum using in vivo microdialysis. 2. Intrastriatal infusion of PCP (1 mM) via a microdialysis probe did not alter the basal extracellular levels of either glutamate or GABA. Addition of N-methyl-D-aspartic acid (NMDA; 0.2, 0.5 and 1 mM) to the perfusion medium resulted in a dose-dependent increase in extracellular levels of glutamate. 3. Intrastriatal infusion of tetrodotoxin (0.1, 1, 10 microM), a highly selective blocker of voltage-dependent sodium channels, significantly attenuated the NMDA-stimulated release of glutamate, suggesting that NMDA-evoked release of glutamate originated from the neuronal pool and that the increase of striatal glutamate level was regulated indirectly via NMDA receptors. 4. The NMDA-induced release of glutamate was reduced significantly by pretreatment with local PCP (1 mM). Dizocilpine (MK801; 0.2 mM), a non-competitive NMDA antagonist, completely inhibited the NMDA-stimulated release of glutamate. 5. These results suggest that, in the striatum, PCP inhibits corticostriatal glutamatergic neurotransmission by inhibiting the release of glutamate probably via postsynaptic NMDA receptors.