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纹状体内注射多巴胺可逆转6-羟基多巴胺损伤大鼠中D2-多巴胺受体的代偿性增加。

Intrastriatal dopamine infusion reverses compensatory increases in D2-dopamine receptors in the 6-OHDA lesioned rat.

作者信息

Woiciechowsky C, Guilarte T R, May C H, Vesper J, Wagner H N, Vogel S

机构信息

Department of Neurosurgery, Humboldt-University, Medical School (Charité), Berlin, Germany.

出版信息

Neurodegeneration. 1995 Jun;4(2):161-9. doi: 10.1006/neur.1995.0020.

DOI:10.1006/neur.1995.0020
PMID:7583680
Abstract

Direct infusion of dopamine into the corpus striatum has been proposed as a potential approach for the treatment of Parkinson's disease. The present study examined the effect of intrastriatal dopamine infusion on D2-dopamine receptors in the 6-hydroxydopamine (6-OHDA) lesioned rat brain. The completeness of the 6-OHDA-induced nigrostriatal injury was confirmed using [3H]-mazindol autoradiography and apomorphine-induced behaviour. Intrastriatal infusion of three different dopamine doses significantly reduced the apomorphine-induced behaviour. [3H]-spiperone autoradiography performed one day after the termination of dopamine infusion into the striatum revealed a dramatic reduction of D2-dopamine receptor binding. The mean +/- SEM percent reduction of D2 receptor binding in the affected areas of the striatum was 28.8 +/- 1.0% for 4.74 micrograms dopamine/h infusion rate, 35.0 +/- 1.6% for 9.48 micrograms dopamine/h infusion rate and 33.3 +/- 5.0% for 14.22 micrograms dopamine/h infusion rate when compared to the unlesioned side. Infusion of vehicle alone did not have any effect. The present results support the concept that intrastriatal dopamine infusion may be a useful therapeutic approach for the treatment of Parkinson's disease.

摘要

将多巴胺直接注入纹状体已被提议作为治疗帕金森病的一种潜在方法。本研究检测了纹状体内注入多巴胺对6-羟基多巴胺(6-OHDA)损伤大鼠脑内D2-多巴胺受体的影响。使用[3H]-吗茚酮放射自显影术和阿扑吗啡诱导的行为来确认6-OHDA诱导的黑质纹状体损伤的完整性。向纹状体内注入三种不同剂量的多巴胺可显著减少阿扑吗啡诱导的行为。在终止向纹状体注入多巴胺一天后进行的[3H]-螺哌隆放射自显影术显示D2-多巴胺受体结合显著减少。与未损伤侧相比,多巴胺注入速率为4.74微克/小时时,纹状体受影响区域D2受体结合的平均减少百分比±标准误为28.8±1.0%;多巴胺注入速率为9.48微克/小时时为35.0±1.6%;多巴胺注入速率为14.22微克/小时时为33.3±5.0%。仅注入溶剂没有任何效果。目前的结果支持这样一种观点,即纹状体内注入多巴胺可能是治疗帕金森病的一种有效治疗方法。

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