THE EFFECTS OF HALOPERIDOL AND CLOZAPINE ON EXTRACELLULAR GABA LEVELSIN THE PREFRONTAL CORTEX OF THE RAT - AN IN-VIVO MICRODIALYSIS STUDY

Recent electrophysiological and pharmacological data indicate that dop amine enhances the activity of interneurons in the prefrontal cortex ( PFC) and induces the release of GABA from these cells. We used in vivo microdialysis to examine the effects of two dopamine receptor antagon ists on GABA release in the prefrontal cortex of awake, freely moving rats. Depolarization accomplished by local perfusion of potassium chlo ride or veratradine markedly increased extracellular GABA levels in th e RES. In contrast, local perfusion of TTX reduced extracellular GABA levels in the PFC, These data indicate that extracellular GABA is deri ved in part from neurons, and that extracellular levels of the inhibit ory amino acid are impulse dependent. The acute administration of halo peridol weakly but significantly decreased extracellular GABA levels i n the PFC; no effect of haloperidol on striatal extracellular GABA lev els was observed. Systemic administration of the atypical antipsychoti c drug clozapine markedly reduced extracellular GABA levels in the PFC , but did not alter striatal GABA levels. Thus, release of GABA from i nterneurons in the RED is inhibited by two antipsychotic drugs. These data may suggest that different D-2-like dopamine receptors are locali zed to pyramidal and nonpyramidal neurons in the cortex.