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

We have investigated the effects of perfusion of the N-methyl-D-aspartate ( NMDA) receptor antagonist 3-((R)-2-carboxypiperazin-4-yl)-propyl-1 -phospho nic acid (CPP) and the alpha -amino-3-hydroxy-5-methyl-isoxarole-4-propioni c acid (AMPA)/ kainate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) on the endogenous glutamate-evoked changes of extracellular dopamin e and alpha -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 extr acellular 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 muM (n = 8; p < 0.001), 4.70 +/- 0.92 nM (n = 6; p < 0.001) and 0. 36 +/- 0.08 muM (0 = 8; p < 0.001), respectively. Perfusion of the NMDA-rec eptor 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). Perf usion of the AMPA-receptor antagonist DNQX did not attenuate the increases of GABA. These results suggest a differential mediation of ionotropic gluta matergic receptors in the actions of endogenous glutamate on extracellular concentration of dopamine and GABA. (C) 2001 Elsevier Science Inc.