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美金刚对大鼠纹状体和伏隔核多巴胺代谢影响的体内研究。

In vivo studies on the effects of memantine on dopamine metabolism in the striatum and n. accumbens of the rat.

作者信息

Clement H W, Grote C, Svensson L, Engel J, Zöfel P, Wesemann W

机构信息

Department of Neurochemistry, Philipps University, Marburg/Lahn, Federal Republic of Germany.

出版信息

J Neural Transm Suppl. 1995;46:107-15.

PMID:8821046
Abstract

The action of the amantadine derivative memantine on the dopamine metabolism in the striatum and the n. accumbens of the rat was studied in vivo with different voltammetrical techniques. It was shown by differential pulse voltammetry that memantine enhanced extracellular levels of dopamine (DA) in the striatum of the anaesthetized rat, whereas an increase of 3,4 dihydroxyphenylacetic acid (DOPAC) could be observed only under freely moving conditions using square wave voltammetry. Under chloral hydrate anaesthesia the effect of memantine on extracellular DOPAC levels in the striatum and the n. accumbens was compared with MK-801, a well-known non-competitive NMDA-antagonist. Memantine did not affect striatal DOPAC concentrations under these conditions whereas MK-801 reduced the DOPAC signal. In the n. accumbens memantine enhanced the levels of extracellular DOPAC, while after MK-801 the signal was only slightly different from control. These findings suggest that in addition to its NMDA receptor antagonism, memantine affects dopaminergic transmission also by other mechanisms.

摘要

利用不同的伏安法技术在体内研究了金刚烷胺衍生物美金刚对大鼠纹状体和伏隔核中多巴胺代谢的作用。差分脉冲伏安法表明,美金刚可提高麻醉大鼠纹状体中多巴胺(DA)的细胞外水平,而仅在自由活动条件下使用方波伏安法才能观察到3,4-二羟基苯乙酸(DOPAC)增加。在水合氯醛麻醉下,将美金刚对纹状体和伏隔核中细胞外DOPAC水平的影响与著名的非竞争性NMDA拮抗剂MK-801进行了比较。在这些条件下,美金刚不影响纹状体DOPAC浓度,而MK-801降低了DOPAC信号。在伏隔核中,美金刚提高了细胞外DOPAC水平,而在MK-801作用后,信号与对照组仅略有不同。这些发现表明,除了其NMDA受体拮抗作用外,美金刚还通过其他机制影响多巴胺能传递。

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