Blanchet F, Kemel M L, Gauchy C, Desban M, Perez S, Glowinski J
INSERM U114, Collège de France, Paris, France.
Neuroscience. 1997 Nov;81(1):113-27. doi: 10.1016/s0306-4522(97)00198-x.
The N-methyl-D-aspartate-evoked release of [3H]acetylcholine previously formed from [3H]choline was estimated in striosome- (identified by [3H]naloxone binding) or matrix-enriched areas of the rat striatum using an in vitro microsuperfusion procedure. Experiments were performed in either the absence or the presence of dopaminergic and/or GABAergic receptor antagonists. Although the cell bodies of the cholinergic interneurons were mainly found in the matrix, in the absence of magnesium, N-methyl-D-aspartate (50 microM) stimulated the release of [3H]acetylcholine in both striatal compartments. These responses were blocked by either magnesium, dizocilpine maleate, 7-chlorokynurenate or tetrodotoxin. N-Methyl-D-aspartate responses were concentration-dependent, but the 1 mM N-methyl-D-aspartate response was higher in striosomes than in the matrix. The co-application of D-serine (10 microM) enhanced the 10 microM N-methyl-D-aspartate response in both compartments, but reduced those induced by 1 mM N-methyl-D-aspartate, this reduction being higher in striosomes. The blockade of dopaminergic transmission with the D2 and D1 dopaminergic receptor antagonists, (-)-sulpiride (1 microM) and SCH23390 (1 microM), was without effect on the 50 microM N-methyl-D-aspartate-evoked release of [3H]acetylcholine, but markedly enhanced the 1 mM N-methyl-D-aspartate+D-serine-evoked response in striosomes and to a lesser extent in the matrix. Disinhibitory responses of similar amplitude were observed not only in striosomes but also in the matrix when (-)-sulpiride was used alone, while SCH23390 alone enhanced the 1 mM N-methyl-D-aspartate+D-serine response only in striosomes and to a lower extent than (-)-sulpiride. These results indicate that D2 receptors are mainly involved in the inhibitory effect of dopamine on the 1 mM N-methyl-D-aspartate+D-serine-evoked release of [3H]acetylcholine. They also show that the stimulation of D1 receptors can either reduce (striosomes) or enhance (matrix) this response, since in the latter case the effect induced by the combined application of the D1 and D2 receptor antagonists was smaller than that observed with the D2 receptor antagonist alone. Indicating that released GABA facilitates N-methyl-D-aspartate responses, the blockade of GABAA receptors with bicuculline (5 microM) reduced the 50 microM N-methyl-D-aspartate-evoked release of [3H]acetylcholine in both striatal compartments and the 1 mM N-methyl-D-aspartate+D-serine response in the matrix. These effects result from an inhibition by GABA of the evoked release of dopamine, since the reducing effects of bicuculline on N-methyl-D-aspartate responses were not observed under the complete blockade of dopaminergic transmission by the D1 and D2 receptor antagonists. Further demonstrating a facilitatory role of GABA in the control of N-methyl-D-aspartate-evoked release of [3H]acetylcholine, in the presence of bicuculline, (-)-sulpiride and SCH23390 alone or in combination enhanced, in both compartments, the responses induced not only by 1 mM N-methyl-D-aspartate+D-serine, but also by 50 microM N-methyl-D-aspartate.
利用体外微量灌注法，在大鼠纹状体富含纹状体小体（通过[3H]纳洛酮结合鉴定）或基质的区域中，评估了由[3H]胆碱预先形成的[3H]乙酰胆碱经N-甲基-D-天冬氨酸诱发的释放。实验在不存在或存在多巴胺能和/或GABA能受体拮抗剂的情况下进行。虽然胆碱能中间神经元的细胞体主要存在于基质中，但在无镁的情况下，N-甲基-D-天冬氨酸（50微摩尔）刺激了两个纹状体区室中[3H]乙酰胆碱的释放。这些反应被镁、马来酸氯氮平、7-氯犬尿氨酸或河豚毒素阻断。N-甲基-D-天冬氨酸反应呈浓度依赖性，但1毫摩尔N-甲基-D-天冬氨酸在纹状体小体中的反应高于基质中的反应。共同应用D-丝氨酸（10微摩尔）增强了两个区室中10微摩尔N-甲基-D-天冬氨酸的反应，但降低了1毫摩尔N-甲基-D-天冬氨酸诱导的反应，纹状体小体中的这种降低更为明显。用D2和D1多巴胺能受体拮抗剂（-）-舒必利（1微摩尔）和SCH23390（1微摩尔）阻断多巴胺能传递，对50微摩尔N-甲基-D-天冬氨酸诱发的[3H]乙酰胆碱释放没有影响，但显著增强了1毫摩尔N-甲基-D-天冬氨酸+D-丝氨酸在纹状体小体中诱发的反应，在基质中的增强程度较小。当单独使用（-）-舒必利时，不仅在纹状体小体中，而且在基质中都观察到了类似幅度的去抑制反应，而单独使用SCH23390仅增强了1毫摩尔N-甲基-D-天冬氨酸+D-丝氨酸在纹状体小体中的反应，且增强程度低于（-）-舒必利。这些结果表明，D2受体主要参与多巴胺对1毫摩尔N-甲基-D-天冬氨酸+D-丝氨酸诱发的[3H]乙酰胆碱释放的抑制作用。它们还表明，D1受体的刺激可以降低（纹状体小体）或增强（基质）这种反应，因为在后一种情况下，联合应用D1和D2受体拮抗剂诱导的效应小于单独使用D2受体拮抗剂时观察到的效应。用荷包牡丹碱（5微摩尔）阻断GABAA受体可降低两个纹状体区室中50微摩尔N-甲基-D-天冬氨酸诱发的[3H]乙酰胆碱释放以及基质中1毫摩尔N-甲基-D-天冬氨酸+D-丝氨酸的反应，这表明释放的GABA促进了N-甲基-D-天冬氨酸反应。这些效应是由于GABA抑制了诱发的多巴胺释放，因为在D1和D2受体拮抗剂完全阻断多巴胺能传递的情况下，未观察到荷包牡丹碱对N-甲基-D-天冬氨酸反应的降低作用。在存在荷包牡丹碱的情况下，进一步证明了GABA在控制N-甲基-D-天冬氨酸诱发的[3H]乙酰胆碱释放中的促进作用，单独或联合使用（-）-舒必利和SCH23390增强了两个区室中不仅由1毫摩尔N-甲基-D-天冬氨酸+D-丝氨酸诱发的反应，而且还有50微摩尔N-甲基-D-天冬氨酸诱发的反应。
