Lorenc-Koci E, Konieczny J, Wolfarth S
Department of Neuropsychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12, Smetna St., PL-31-343 Kraków, Poland.
Brain Res. 1998 May 18;793(1-2):315-20. doi: 10.1016/s0006-8993(98)00240-6.
The aim of the present study was to assess the contribution of the glycine site of NMDA receptors in the striatum to the regulation of muscle tone. Muscle tone was examined using a combined mechanoand electromyographic method, which measured simultaneously the muscle resistance (MMG) of the rat's hind foot to passive extension and flexion in the ankle joint and the electromyographic activity (EMG) of the antagonistic muscles of that joint: gastrocnemius and tibialis anterior. Muscle rigidity was induced by haloperidol (2.5 mg/kg i.p.). 5,7-dichlorokynurenic acid (5,7-DCKA), a selective glycine site antagonist, injected in doses of 2.5 and 4.5 microg/0.5 microl bilaterally, into the rostral region of the striatum, decreased both the haloperidol-induced muscle rigidity (MMG) and the enhanced electromyographic activity (EMG). 5,7-DCKA injected bilaterally in a dose of 4.5 microg/0.5 microl into the intermediate-caudal region of the striatum of rats not pretreated with haloperidol had no effect on the muscle tone. The present results suggest that blockade of the glycine site of NMDA receptors in the rostral part of the striatum may be mainly responsible for the antiparkinsonian action of this drug.
本研究的目的是评估纹状体中N-甲基-D-天冬氨酸(NMDA)受体的甘氨酸位点对肌张力调节的作用。使用机械和肌电图联合方法检测肌张力,该方法同时测量大鼠后足对踝关节被动伸展和屈曲的肌肉阻力(MMG)以及该关节拮抗肌(腓肠肌和胫骨前肌)的肌电活动(EMG)。用氟哌啶醇(2.5mg/kg腹腔注射)诱导肌肉强直。5,7-二氯犬尿氨酸(5,7-DCKA),一种选择性甘氨酸位点拮抗剂,以2.5和4.5μg/0.5μl的剂量双侧注射到纹状体的嘴侧区域,可降低氟哌啶醇诱导的肌肉强直(MMG)和增强的肌电活动(EMG)。在未用氟哌啶醇预处理的大鼠纹状体中尾区域双侧注射4.5μg/0.5μl剂量的5,7-DCKA对肌张力没有影响。目前的结果表明,纹状体嘴侧部分NMDA受体甘氨酸位点的阻断可能是该药物抗帕金森病作用的主要原因。