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突触前控制 5-羟色胺对纹状体多巴胺功能的影响。

Presynaptic control of serotonin on striatal dopamine function.

机构信息

Unité Mixte de Recherche Centre National de la Recherche Scientifique 5227, Université Victor Segalen Bordeaux 2, Bordeaux, France.

出版信息

Psychopharmacology (Berl). 2011 Feb;213(2-3):213-42. doi: 10.1007/s00213-010-2029-y. Epub 2010 Oct 16.

DOI:10.1007/s00213-010-2029-y
PMID:20953589
Abstract

RATIONALE

The influences of the serotonergic system on dopamine (DA) neuron activity have received considerable attention during the last three decades due to the real opportunity to improve disorders related to central DA neuron dysfunctions such as Parkinson's disease, schizophrenia, or drug abuse with serotonergic drugs. Numerous biochemical and behavioral data indicate that serotonin (5-HT) affects dopaminergic terminal function in the striatum.

OBJECTIVE

The authors propose a thorough examination of data showing controversial effects induced by striatal 5-HT on dopaminergic activity.

RESULTS

Inhibitory and excitatory effects of exogenous 5-HT have been reported on DA release and synthesis, involving various striatal 5-HT receptors. 5-HT also promotes an efflux of DA through reversal of the direction of DA transport. By analogy with the mechanism of action described for amphetamine, the consequences of 5-HT entering DA terminals might explain both the excitatory and inhibitory effects of 5-HT on presynaptic DA terminal activity, but the physiological relevance of this mechanism is far from clear. The recent data suggest that the endogenous 5-HT system affects striatal DA release in a state-dependent manner associated with the conditional involvement of various 5-HT receptors such as 5-HT(2A), 5-HT(2C), 5-HT(3), and 5-HT(4) receptors.

CONCLUSION

Methodological and pharmacological issues have prevented a comprehensive overview of the influence of 5-HT on striatal DA activity. The distribution of striatal 5-HT receptors and their restricted influence on DA neuron activity suggest that the endogenous 5-HT system exerts multiple and subtle influences on DA-mediated behaviors.

摘要

原理

由于有机会用血清素（5-HT）类药物改善与中脑多巴胺（DA）神经元功能障碍相关的疾病，如帕金森病、精神分裂症或药物滥用，因此在过去三十年中，人们对 5-HT 系统对 DA 神经元活性的影响给予了相当的关注。大量生化和行为数据表明，5-HT 会影响纹状体中的多巴胺能末梢功能。

目的

作者提出了对显示纹状体 5-HT 对多巴胺活性产生争议性影响的数据进行全面检查。

结果

已报道外源性 5-HT 对 DA 释放和合成具有抑制和兴奋作用，涉及各种纹状体 5-HT 受体。5-HT 还通过逆转 DA 转运的方向促进 DA 的外排。与描述的安非他命作用机制类似，5-HT 进入 DA 末梢的后果可能解释 5-HT 对突触前 DA 末梢活动的兴奋和抑制作用，但该机制的生理相关性尚不清楚。最近的数据表明，内源性 5-HT 系统以与各种 5-HT 受体（如 5-HT2A、5-HT2C、5-HT3 和 5-HT4 受体）的条件参与相关的状态依赖性方式影响纹状体 DA 释放。

结论

方法学和药理学问题阻碍了对 5-HT 对纹状体 DA 活性影响的全面概述。纹状体 5-HT 受体的分布及其对 DA 神经元活性的限制影响表明，内源性 5-HT 系统对 DA 介导的行为施加了多种微妙的影响。

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