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重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。

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

作者信息

Brannan T, Martínez-Tica J, Yahr M D

机构信息

Department of Neurology, Mount Sinai School of Medicine, New York, NY.

出版信息

J Neural Transm Park Dis Dement Sect. 1993;6(1):35-44. doi: 10.1007/BF02252621.

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.

摘要

据报道,采用电惊厥休克(ECS)进行一个疗程的治疗可使晚期帕金森病患者重新获得左旋多巴的疗效。我们希望确定ECS是否能在帕金森病动物模型中改变左旋多巴和多巴胺的代谢。因此,我们对黑质纹状体多巴胺通路部分受损的大鼠每隔48小时重复给予8次ECS,并使用脑微透析技术监测纹状体内多巴胺及其代谢产物(3,4-二羟基苯乙酸[DOPAC]和高香草酸[HVA])的细胞外浓度。对照组动物接受假ECS治疗。与假ECS组相比,接受重复ECS治疗的动物基础多巴胺水平降低了20%。另一方面,接受重复ECS治疗的动物DOPAC水平升高了84%。两组的HVA水平相当。给予左旋多巴后,对照组动物和先前接受重复ECS治疗的动物中多巴胺和HVA水平的升高幅度相同。接受重复ECS治疗的大鼠中DOPAC浓度始终更高。急性给予ECS时,多巴胺水平升高390%,并在75分钟内恢复至基线值,DOPAC和HVA未发生变化,5-羟吲哚乙酸(5HIAA)水平降低30%。我们得出以下结论:1)急性给予ECS可使纹状体多巴胺产生短暂而显著的释放;2)重复给予ECS可重置基础多巴胺释放水平,这一发现与ECS诱导的多巴胺受体超敏反应相符;3)无论是单次还是重复给予ECS,对外源性给予的左旋多巴生成多巴胺或HVA均无重大影响,尽管DOPAC生成有明显增加的趋势。ECS可能通过增强多巴胺受体敏感性发挥其假定的抗帕金森病作用。

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