Segovia G, Mora F
Department of Physiology, Faculty of Medicine, Universidad Complutense, Madrid, Spain.
Brain Res Bull. 2001 Jan 15;54(2):153-7. doi: 10.1016/s0361-9230(00)00432-9.
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 alpha-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 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 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 microM (n = 8; p < 0.001), 4.70 +/- 0.92 nM (n = 6; p < 0.001) and 0.36 +/- 0.08 microM (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.
我们研究了灌注N-甲基-D-天冬氨酸（NMDA）受体拮抗剂3-((R)-2-羧基哌嗪-4-基)-丙基-1-膦酸（CPP）和α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）/海人藻酸受体拮抗剂6,7-二硝基喹喔啉-2,3-二酮（DNQX）对清醒大鼠伏隔核中内源性谷氨酸诱发的细胞外多巴胺和α-氨基丁酸（GABA）变化的影响。在伏隔核局部注入谷氨酸摄取抑制剂L-反式-脯氨酸-2,4-二羧酸会导致细胞外谷氨酸、多巴胺和GABA浓度升高。在4 mM的剂量下，细胞外谷氨酸、多巴胺和GABA的升高分别为3.73±0.46微摩尔/升（n = 8；p < 0.001）、4.70±0.92纳摩尔/升（n = 6；p < 0.001）和0.36±0.08微摩尔/升（n = 8；p < 0.001）。灌注NMDA受体拮抗剂CPP使多巴胺的升高减弱了90%（n = 5；p < 0.001），但使GABA的升高增强了70%（n = 7；p < 0.01）。灌注AMPA受体拮抗剂DNQX并没有减弱GABA的升高。这些结果表明离子型谷氨酸能受体在内源性谷氨酸对细胞外多巴胺和GABA浓度的作用中存在差异介导。
