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在前腹侧被盖区阻断GABA(A) 受体可增加大鼠伏隔核中多巴胺的细胞外水平。

GABA(A) receptor blockade in the anterior ventral tegmental area increases extracellular levels of dopamine in the nucleus accumbens of rats.

作者信息

Ikemoto S, Kohl R R, McBride W J

机构信息

Institute of Psychiatric Research, Department of Psychiatry and Program in Medical Neurobiology, Indiana University School of Medicine, Indianapolis 46202-4887, U.S.A.

出版信息

J Neurochem. 1997 Jul;69(1):137-43. doi: 10.1046/j.1471-4159.1997.69010137.x.

Abstract

Previously, it was shown that microinfusion of the GABA(A) antagonist picrotoxin into the anterior ventral tegmental area (VTA) is reinforcing. It was hypothesized that this reinforcing effect of picrotoxin in the anterior VTA is mediated, at least in part, by the activation of the mesoaccumbens dopamine (DA) system. The objective of the present study was to determine if blockade of GABA(A) receptors in the anterior VTA can increase extracellular levels of DA in the nucleus accumbens (ACB), using an in vivo microdialysis technique in freely moving rats. Concentrations of picrotoxin (40, 80, and 160 microM) that had previously been shown to produce a reinforcing effect increased the extracellular levels of DA and its major metabolites in the ACB. The increased extracellular DA levels induced by intra-VTA injection of picrotoxin was markedly attenuated by coadministration with the GABA(A) agonist muscimol, whereas intra-VTA injection of muscimol alone did not have an apparent effect on extracellular DA levels in the ACB. Microinjection of another GABA(A) antagonist, bicuculline, into the anterior VTA also increased the extracellular release of DA in the ACB. These results suggest that DA neurons projecting from the anterior VTA to the ACB are tonically inhibited by GABA through its actions at the GABA(A) receptors.

摘要

先前的研究表明,将GABA(A)拮抗剂印防己毒素微量注入腹侧被盖区(VTA)前部具有强化作用。据推测,印防己毒素在前部VTA的这种强化作用至少部分是由中脑伏隔核多巴胺(DA)系统的激活介导的。本研究的目的是利用自由活动大鼠的体内微透析技术,确定前部VTA中GABA(A)受体的阻断是否能增加伏隔核(ACB)中DA的细胞外水平。先前已证明能产生强化作用的印防己毒素浓度(40、80和160微摩尔)增加了ACB中DA及其主要代谢产物的细胞外水平。VTA内注射印防己毒素诱导的细胞外DA水平升高与GABA(A)激动剂蝇蕈醇共同给药时明显减弱,而单独VTA内注射蝇蕈醇对ACB中的细胞外DA水平没有明显影响。向前部VTA微量注射另一种GABA(A)拮抗剂荷包牡丹碱也增加了ACB中DA的细胞外释放。这些结果表明,从前部VTA投射到ACB的DA神经元通过GABA在GABA(A)受体上的作用受到张力性抑制。

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