Involvement of NMDA and AMPA/kainate receptors in the effects of endogenous glutamate on extracellular concentrations of dopamine and GABA in the nucleus accumbens of the awake rat

Abstract

We have investigated the effects of perfusion of the N-methyl-D-aspartate (NMDA) receptor antagonist 3-((R)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and the α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA)/kainate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) on the endogenous glutamate-evoked changes of extracellular dopamine and α-aminobutyric acid (GABA) in the nucleus accumbens of the awake rat. Local infusion of the glutamate uptake inhibitor L- trans-pyrrolidine-2,4-dicarboxilic acid in the nucleus accumbens produced an increase in extracellular concentrations of glutamate, dopamine, and GABA. At the dose of 4 mM, the increase of extracellular glutamate, dopamine, and GABA were 3.73 ± 0.46 μM ( n = 8; p < 0.001), 4.70 ± 0.92 nM ( n = 6; p < 0.001) and 0.36 ± 0.08 μM ( n = 8; p < 0.001), respectively. Perfusion of the NMDA-receptor antagonist CPP attenuated the increases of dopamine by 90% ( n = 5; p < 0.001), but enhanced the increases of GABA by 70% ( n = 7; p < 0.01). Perfusion of the AMPA-receptor antagonist DNQX did not attenuate the increases of GABA. These results suggest a differential mediation of ionotropic glutamatergic receptors in the actions of endogenous glutamate on extracellular concentration of dopamine and GABA.