Effects of endogenous glutamate on extracellular concentrations of GABA, dopamine, and dopamine metabolites in the prefrontal cortex of the freely moving rat: Involvement of NMDA and AMPA/KA receptors

Using microdialysis, interactions between endogenous glutamate, dopamine, a nd GABA were investigated in the medial prefrontal cortex of the freely mov ing rat. Interactions between glutamate and other neurotransmitters in the prefrontal cortex had already been studied using pharmacological agonists o r antagonists of glutamate receptors. This research investigated whether gl utamate itself, through the increase of its endogenous extracellular concen tration, is able to modulate the extracellular concentrations of GABA and d opamine in the prefrontal cortex. Intracortical infusions of the selective glutamate uptake inhibitor L-trans-pyrrrolidine-2,4-dicarboxylic acid (PDC) were used to increase the endogenous extracellular glutamate. PDC (0.5, 2, 8, 16 and 32 mM) produced a dose-related increase in dialysate glutamate i n a range of 1-36 mu M. At the dose of 16 mM, PDC increased dialysate gluta mate from 1.25 to 28 mu M PDC also increased extracellular GABA and taurine , but not dopamine; and decreased extracellular concentrations of the dopam ine metabolites DOPAC and HVA. NMDA and AMPA/KA receptor antagonists were u sed to investigate whether the increases of extracellular glutamate were re sponsible for the changes in the release of GABA, and dopamine metabolites. The NMDA antagonist had no effect on the increase of extracellular GABA, b ut blocked the decreases of extracellular DOPAC and HVA, produced by PDC. I n contrast, the AMPA/KA antagonist blocked the increases of extracellular G ABA without affecting the decreases of extracellular DOPAC and HVA produced by PDC. These results suggest that endogenous glutamate acts preferentiall y through NMDA receptors to decrease dopamine metabolism, and through AMPA/ KA receptors to increase GABAergic activity in the medial prefrontal cortex of the awake rat.