Del Arco A, Mora F
Department of Physiology, Faculty of Medicine, University Complutense, Madrid, Spain.
Brain Res Bull. 2000 Oct;53(3):339-45. doi: 10.1016/s0361-9230(00)00353-1.
Using microdialysis, the effects of endogenous dopamine on basal extracellular concentrations of gamma-aminobutyric acid (GABA) and on the increases of GABA produced by glutamate were investigated in the medial prefrontal cortex of the awake rat. The dopamine uptake inhibitor nomifensine (1, 100 and 1000 microM), used to increase extracellular dopamine, produced a dose-related increase of dialysate dopamine (0.1-1 nM) but did not change dialysate concentrations of GABA or glutamate at any dose used. The glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxilic acid (PDC; 0.5 and 2 mM), used to increase extracellular glutamate, produced a dose-related increase of dialysate glutamate (1.5-5.5 microM) and increased dialysate GABA by 125%. When a simultaneous increase of endogenous dopamine and glutamate was produced, the increases of dialysate GABA were significantly higher (185% of baseline) than those produced by glutamate alone. These effects on dialysate GABA were attenuated by the D2 receptor antagonist (-) sulpiride, but not by the D1 receptor antagonist SCH-23390, all of which suggests that extracellular dopamine plays an important role in modulating endogenous glutamate-GABA interactions in the prefrontal cortex of the rat.
利用微透析技术，研究了内源性多巴胺对清醒大鼠内侧前额叶皮质中γ-氨基丁酸（GABA）基础细胞外浓度以及对谷氨酸产生的GABA增加量的影响。用于增加细胞外多巴胺的多巴胺摄取抑制剂诺米芬辛（1、100和1000微摩尔）导致透析液多巴胺呈剂量相关增加（0.1 - 1纳摩尔），但在所使用的任何剂量下均未改变透析液中GABA或谷氨酸的浓度。用于增加细胞外谷氨酸的谷氨酸摄取抑制剂L-反式吡咯烷-2,4-二羧酸（PDC；0.5和2毫摩尔）导致透析液谷氨酸呈剂量相关增加（1.5 - 5.5微摩尔），并使透析液GABA增加了125%。当内源性多巴胺和谷氨酸同时增加时，透析液GABA的增加量显著高于单独由谷氨酸引起的增加量（为基线的185%）。这些对透析液GABA的影响被D2受体拮抗剂（-）舒必利减弱，但未被D1受体拮抗剂SCH-23390减弱，所有这些表明细胞外多巴胺在调节大鼠前额叶皮质中内源性谷氨酸 - GABA相互作用方面发挥着重要作用。
