Behavioral effects of 5-HT2C receptor antagonism in the substantia nigra zona reticulata of the 6-hydroxydopamine-lesioned rat model of Parkinson's disease

被引：72

作者：

Fox, SH ^{[1
]}

Moser, B ^{[1
]}

Brotchie, JM ^{[1
]}

机构：

[1] Univ Manchester, Sch Biol Sci, Div Neurosci 1 124, Manchester M13 9PT, Lancs, England

来源：

EXPERIMENTAL NEUROLOGY | 1998年 / 151卷 / 01期

关键词：

5-HT2C receptor; Parkinson's disease; substantia nigra pars reticulata; kynurenate;

D O I：

10.1006/exnr.1998.6792

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Overactivity of the substantia nigra zona reticulata and the medial segment of the globus pallidus are responsible for the generation of symptoms in Parkinson's disease. Reducing the activity of these regions has been shown to be a viable alternative to dopamine replacement in the symptomatic treatment of Parkinson's disease. 5-HT2C receptors in the substantia nigra zona reticulata are excitatory. In this study we have shown that intracerebral infusion of the selective 5-HT2C receptor antagonist SE 206553 (50 nmol) into the substantia nigra zona reticulata has an antiparkinsonian action in the 6-hydroxydopamine-lesioned rat model of Parkinson's disease. SE 206553 did not affect locomotion when injected into the nonparkinsonian substantia nigra. Furthermore, we have demonstrated that systemic administration of selective 5-HT2C receptor antagonists SE 200646A (20 mg/kg) and SE 206553 (20 mg/kg) can potentiate the antiparkinsonian action of the dopamine D-2 receptor agonist quinpirole in the 6-hydroxydopamine-lesioned rat. Hence, 5-HT2C receptor antagonists may be useful adjuncts to dopamine agonists in the treatment of Parkinson's disease. (C) 1998 Academic Press.

引用

页码：35 / 49

页数：15

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