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NMDA和AMPA谷氨酸受体激活对清醒大鼠纹状体中多巴胺、乙酰胆碱和GABA细胞外浓度的影响:一项微透析研究。

Effects of activation of NMDA and AMPA glutamate receptors on the extracellular concentrations of dopamine, acetylcholine, and GABA in striatum of the awake rat: a microdialysis study.

作者信息

Hernández L F, Segovia G, Mora F

机构信息

Department of Physiology, Faculty of Medicine, University Complutense, Madrid, Spain.

出版信息

Neurochem Res. 2003 Dec;28(12):1819-27. doi: 10.1023/a:1026115607216.

Abstract

The effects of activation of the AMPA and NMDA ionotropic glutamate receptors on the extracellular concentration of dopamine, acetylcholine, (ACh) and GABA in striatum of the awake rat was investigated. Also the levels of DOPAC, HVA, and choline (Ch) were included in this study. Seven to eight days after stereotaxical implantation of a guide-cannulae assembly, microdialysis experiments were performed. The dopamine and ACh content of samples were measured by HPLC coupled to electrochemical detection. GABA was measured using fluorometric detection. Perfusion of AMPA (1, 20, 100 microM) produced a dose-related increase of dopamine and a dose-related decrease of DOPAC and HVA. AMPA 100 microM decreased extracellular concentrations of ACh and increased the extracellular concentration of Ch and GABA. Perfusion of NMDA 500 microM increased the concentration of dopamine and decreased DOPAC and HVA. Also, NMDA 100 microM decreased DOPAC. NMDA 500 microM decreased the extracellular concentrations of ACh and increased the concentrations of Ch and GABA. Perfusion of the AMPA/kainate-antagonist DNQX (100 microM) blocked the effects of AMPA (100 microM) on dopamine, DOPAC, HVA, ACh, and GABA concentrations. Perfusion of the NMDA-antagonist CPP (100 microM) blocked the effects of NMDA 500 microM on dopamine, DOPAC, HVA, ACh, Ch, and GABA concentrations. These results suggest an interaction between glutamate-dopamine-ACh-GABA in striatum of the awake rat.

摘要

研究了激活AMPA和NMDA离子型谷氨酸受体对清醒大鼠纹状体中多巴胺、乙酰胆碱(ACh)和GABA细胞外浓度的影响。本研究还纳入了3,4-二羟基苯乙酸(DOPAC)、高香草酸(HVA)和胆碱(Ch)的水平。在立体定向植入引导套管组件7至8天后,进行了微透析实验。通过与电化学检测联用的高效液相色谱法测量样品中的多巴胺和ACh含量。使用荧光检测法测量GABA。灌注AMPA(1、20、100微摩尔)使多巴胺呈剂量相关增加,DOPAC和HVA呈剂量相关减少。100微摩尔的AMPA降低了ACh的细胞外浓度,增加了Ch和GABA的细胞外浓度。灌注500微摩尔的NMDA增加了多巴胺浓度,降低了DOPAC和HVA。此外,100微摩尔的NMDA降低了DOPAC。500微摩尔的NMDA降低了ACh的细胞外浓度,增加了Ch和GABA的浓度。灌注AMPA/海人酸拮抗剂6,7-二硝基喹喔啉-2,3-二酮(DNQX,100微摩尔)阻断了AMPA(100微摩尔)对多巴胺、DOPAC、HVA、ACh和GABA浓度的影响。灌注NMDA拮抗剂3-(2-羧苯基)哌嗪(CPP,100微摩尔)阻断了500微摩尔的NMDA对多巴胺、DOPAC、HVA、ACh、Ch和GABA浓度的影响。这些结果表明清醒大鼠纹状体中谷氨酸-多巴胺-乙酰胆碱-γ-氨基丁酸之间存在相互作用。

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