Taber M T, Baker G B, Fibiger H C
Department of Psychiatry, University of British Columbia, Vancouver, Canada.
Synapse. 1996 Oct;24(2):165-72. doi: 10.1002/(SICI)1098-2396(199610)24:2<165::AID-SYN8>3.0.CO;2-D.
Intracerebral microdialysis was used to investigate the effects of local application of L-glutamate, N-methyl-D-aspartate, and the glutamate uptake inhibitor 1-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) in the nucleus accumbens (NAc) on extracellular dopamine (DA) concentrations. The effects of locally applied PDC on extracellular glutamate concentrations were also examined. Glutamate produced a concentration-dependent decrease in extracellular DA that could be blocked by concurrent, local application of the broad spectrum ionotropic glutamate receptor antagonist kynurenic acid (KYN:1 mM). N-Methyl-D-aspartate had a concentration-dependent effect on DA release, with a low concentration (0.1 mM) producing a decrease and a higher concentration (1.0 mM) resulting in an increase. Both effects were blocked by KYN. PDC (1 mM) increased extracellular glutamate concentrations to 102% above baseline. The same concentration of PDC decreased extracellular DA concentrations, and coapplication of KYN attenuated this effect. These results indicate that glutamate receptor agonists can have both facilitatory and inhibitory effects on extracellular DA concentrations. However, the effects of PDC indicate that inhibition of DA release is the more physiologically relevant effect. Furthermore, the results of these and other experiments suggest that glutamate's inhibitory effects on DA release in the NAc are not due to direct actions of this excitatory amino acid on DA terminals. A multisynaptic model that accounts for glutamate's actions on DA release is proposed.
采用脑内微透析技术，研究向伏隔核（NAc）局部应用L-谷氨酸、N-甲基-D-天冬氨酸以及谷氨酸摄取抑制剂1-反式-吡咯烷-2,4-二羧酸（PDC）对细胞外多巴胺（DA）浓度的影响。同时也检测了局部应用PDC对细胞外谷氨酸浓度的影响。谷氨酸可使细胞外DA浓度呈浓度依赖性降低，同时局部应用广谱离子型谷氨酸受体拮抗剂犬尿氨酸（KYN：1 mM）可阻断这一效应。N-甲基-D-天冬氨酸对DA释放具有浓度依赖性作用，低浓度（0.1 mM）时导致DA释放减少，高浓度（1.0 mM）时则使DA释放增加。这两种效应均被KYN阻断。PDC（1 mM）可使细胞外谷氨酸浓度升高至基线以上102%。相同浓度的PDC可降低细胞外DA浓度，同时应用KYN可减弱这一效应。这些结果表明，谷氨酸受体激动剂对细胞外DA浓度可产生促进和抑制两种作用。然而，PDC的作用表明抑制DA释放是更具生理相关性的效应。此外，这些实验及其他实验结果提示，谷氨酸对NAc中DA释放的抑制作用并非由于这种兴奋性氨基酸对DA终末的直接作用。本文提出了一个解释谷氨酸对DA释放作用的多突触模型。
