Endogenous dopamine potentiates the effects of glutamate on extracellular GABA in the prefrontal cortex of the freely moving rat

Using microdialysis, the effects of endogenous dopamine on basal extracellu lar concentrations of gamma -aminobutyric acid (GABA) and on the increases of GABA produced by glutamate were investigated in the medial prefrontal co rtex of the awake rat. The dopamine uptake inhibitor nomifensine (1, 100 an d 1000 muM), used to increase extracellular dopamine, produced a dose-relat ed increase of dialysate dopamine (0.1-1 nM) but did not change dialysate c oncentrations of GABA or glutamate at any dose used. The glutamate uptake i nhibitor L-trans-pyrrolidine-2,4-dicarboxilic acid (PDC; 0.5 and 2 mM), use d to increase extracellular glutamate, produced a dose-related increase of dialysate glutamate (1.5-5.5 muM) and increased dialysate GABA by 125%. Whe n a simultaneous increase of endogenous dopamine and glutamate was produced , the increases of dialysate GABA were significantly higher (185% of baseli ne) than those produced by glutamate alone. These effects on dialysate GABA were attenuated by the D2 receptor antagonist (-) sulpiride, but not by th e D1 receptor antagonist SCH-23390, all of which suggests that extracellula r dopamine plays an important role in modulating endogenous glutamate-GABA interactions in the prefrontal cortex of the rat. (C) 2000 Elsevier Science Inc.