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代谢型谷氨酸受体5(mGluR5)的阻断在大鼠中产生抗帕金森氏症样效应。

Blockade of the metabotropic glutamate receptor subtype 5 (mGluR5) produces antiparkinsonian-like effects in rats.

作者信息

Ossowska K, Konieczny J, Wolfarth S, Wierońska J, Pilc A

机构信息

Department of Neuro-Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna St, 31-343 Kraków, Poland.

出版信息

Neuropharmacology. 2001 Sep;41(4):413-20. doi: 10.1016/s0028-3908(01)00083-1.

Abstract

The aim of the present study was to examine a potential beneficial effect of the blockade of metabotropic glutamate receptor subtype 5 (mGluR5) by the selective non-competitive antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP), in models of parkinsonian symptoms in rats. Haloperidol, 0.25, 0.5 and 1mg/kg ip, was used to induce hypolocomotion, catalepsy and muscle rigidity, respectively. The locomotor activity was estimated by an open-field test, the catalepsy -- by a 9-cm cork test. The muscle rigidity was measured as an increased resistance of a hind leg to passive extension and flexion at the ankle joint. Additionally, increases in the electromyographic activity were recorded in the gastrocnemius and tibialis anterior muscles. MPEP (1.0-10mg/kg ip) inhibited the muscle rigidity, electromyographic activity, hypolocomotion and catalepsy induced by haloperidol. MPEP administered alone (5mg/kg ip) did not induce catalepsy, nor did it influence the muscle tone or locomotor activity in rats. The present results suggest that blockade of mGluR5 receptors may be important to amelioration of both parkinsonian akinesia and muscle rigidity.

摘要

本研究的目的是在大鼠帕金森氏症症状模型中,检测选择性非竞争性拮抗剂2-甲基-6-(苯乙炔基)吡啶(MPEP)对代谢型谷氨酸受体5(mGluR5)的阻断作用是否具有潜在益处。腹腔注射0.25、0.5和1mg/kg的氟哌啶醇,分别用于诱导运动减少、僵住症和肌肉强直。通过旷场试验评估运动活性,通过9厘米软木塞试验评估僵住症。肌肉强直通过后腿对踝关节被动伸展和屈曲的阻力增加来测量。此外,记录腓肠肌和胫骨前肌肌电图活性的增加。MPEP(1.0 - 10mg/kg腹腔注射)可抑制氟哌啶醇诱导的肌肉强直、肌电图活性、运动减少和僵住症。单独给予MPEP(5mg/kg腹腔注射)不会诱导僵住症,也不会影响大鼠的肌张力或运动活性。目前的结果表明,阻断mGluR5受体可能对改善帕金森氏症的运动不能和肌肉强直都很重要。

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