Effect of repeated electroconvulsive shock on striatal L-dopa and dopamine metabolism: an in vivo study.

T Brannan, J Martínez-Tica, M D Yahr
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引用次数: 8

Abstract

A course of treatments with electroconvulsive shock (ECS) has been reported to reestablish L-dopa efficacy in patients with advanced Parkinson's disease. We wished to determine if ECS could modify L-dopa and dopamine metabolism in an animal model of Parkinson's disease. Therefore, we administered repeated ECS (8 ECS at 48 hr intervals) to rats with partial destruction of the nigrostriatal dopamine pathway and used the cerebral microdialysis technique to monitor extracellular concentrations of dopamine and dopamine metabolites (DOPAC and HVA) in the corpus striatum. The control group of animals received sham-ECS treatments. Basal dopamine levels were decreased by 20% in animals receiving repeated-ECS versus sham-ECS. DOPAC levels, on the other hand, were increased by 84% in animals receiving repeated-ECS. HVA levels were equal in the two groups. Following L-dopa administration, dopamine and HVA levels increased equally in control animals and animals which had previously received repeated-ECS. DOPAC concentrations were uniformly greater in rats receiving repeated-ECS. When ECS was administered acutely, dopamine levels increased 390% and returned to baseline values in 75 minutes, DOPAC and HVA were unchanged, and 5HIAA levels decreased 30%. We conclude that 1) acute ECS administration produces a transient, marked release of striatal dopamine and 2) repeated ECS can reset the level of basal dopamine release, a finding compatible with ECS-induced dopamine receptor supersensitivity, and 3) neither single nor repeated administration of ECS has a major effect on the formation of dopamine or HVA from exogenously administered L-dopa although there was a strong tendency for increased DOPAC formation. ECS may exert its putative antiparkinsonian effect by enhancing dopamine receptor sensitivity.

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反复电休克对纹状体左旋多巴和多巴胺代谢的影响:一项体内研究。
据报道,一个疗程的电休克(ECS)治疗可以重建左旋多巴对晚期帕金森病患者的疗效。我们希望确定ECS是否可以改变帕金森病动物模型中的左旋多巴和多巴胺代谢。因此,我们对黑质纹状体多巴胺通路部分破坏的大鼠进行重复ECS(8次ECS,间隔48小时),并使用脑微透析技术监测纹状体中多巴胺和多巴胺代谢物(DOPAC和HVA)的细胞外浓度。对照组动物接受假ecs治疗。与假ecs相比,重复ecs动物的基础多巴胺水平下降了20%。另一方面,在接受重复ecs的动物中,DOPAC水平增加了84%。两组HVA水平相等。在给予左旋多巴后,对照动物和先前接受重复ecs的动物的多巴胺和HVA水平增加相同。接受重复ecs的大鼠DOPAC浓度均较高。当急性给予ECS时,多巴胺水平增加390%并在75分钟内恢复到基线值,DOPAC和HVA保持不变,5HIAA水平下降30%。我们得出的结论是:1)急性ECS会产生短暂的纹状体多巴胺的显著释放;2)重复ECS可以重置基底多巴胺的释放水平,这与ECS诱导的多巴胺受体超敏感性相一致;3)单次或多次ECS对外源性左旋多巴的多巴胺或HVA的形成都没有重大影响,尽管DOPAC的形成有强烈的增加趋势。ECS可能通过增强多巴胺受体的敏感性来发挥其抗帕金森病的作用。
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