Abstract

The dopamine system in the limbic-prefrontal cortex has been assumed to play an important role in the cognitive dysfunction of schizophrenia and phencyclidine (PCP)-induced psychosis. In the present study, the role of metabotropic glutamate (mGlu) receptor subtypes on PCP-induced cortical dopamine release was investigated using the microdialysis technique. Infusion of 50 and 100 μM of non-selective mGlu receptor agonist trans-(1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid inhibited PCP-induced dopamine release, while the basal dopamine level was not significantly affected. A similar inhibition of PCP-induced dopamine release was observed with 100 and 500 μM of selective group I mGlu receptor agonist, (+)-3-hydroxy-phenylglycine. On the other hand, infusion of 10 μM of selective group II mGlu receptor agonist, 2-(2, 3-dicarboxycyclopropyl)-glycine, enhanced the PCP-induced dopamine increase. These results suggest that group I and II mGlu receptors exert opposite modulations on the PCP-induced dopamine release.

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