Ossowska K, Lorenc-Koci E, Konieczny J, Wolfarth S
Department of Neuro-Psychopharmacology, Polish Academy of Sciences, Kraków, Poland.
Amino Acids. 1998;14(1-3):11-5. doi: 10.1007/BF01345236.
The aim of the study was to examine the effect of antagonists of the NMDA receptor on the parkinsonian-like muscle rigidity in rats. Reserpine and haloperidol increased the muscle resistance of the hind foot to passive movements, as well as the reflex electromyographic (EMG) activity in the gastroenemius and tibialis anterior muscles. MK-801 (0.32-1.28 mg/kg s.c.), an uncompetitive antagonist of the NMDA receptor, and L-701,324 (5-40 mg/kg i.p.), an antagonist of the glycine site, reduced the muscle tone and the reflex EMG activity enhanced by reserpine or haloperidol. AP-5 (2 and 5 micrograms/0.5 microliter), a competitive antagonist of the NMDA receptor, and 5,7-dichlorokynurenic acid (1.0-4.5 micrograms/0.5 microliter), the glycine site antagonist injected bilaterally into the rostral striatum, inhibited the muscle rigidity induced by haloperidol. In contrast, AP-5, injected alone bilaterally into the intermediate-caudal striatum induced muscle rigidity. The present results suggest that: (1) the inhibitory effect of the NMDA receptor antagonists on the parkinsonian-like muscle rigidity depends, at least partly, on their action on the rostral striatum; (2) the blockade of NMDA receptors in the intermediate-caudal striatum may reduce the beneficial impact of these compounds.
本研究的目的是检测N-甲基-D-天冬氨酸（NMDA）受体拮抗剂对大鼠帕金森样肌肉僵硬的影响。利血平和氟哌啶醇增加了后足对被动运动的肌肉阻力，以及腓肠肌和胫前肌的反射性肌电图（EMG）活动。非竞争性NMDA受体拮抗剂MK-801（0.32 - 1.28毫克/千克，皮下注射）和甘氨酸位点拮抗剂L-701,324（5 - 40毫克/千克，腹腔注射）降低了由利血平或氟哌啶醇增强的肌张力和反射性EMG活动。NMDA受体竞争性拮抗剂AP-5（2和5微克/0.5微升）和双侧注射到吻侧纹状体的甘氨酸位点拮抗剂5,7-二氯犬尿喹啉酸（1.0 - 4.5微克/0.5微升）抑制了氟哌啶醇诱导的肌肉僵硬。相反，双侧单独注射到中间-尾侧纹状体的AP-5诱导了肌肉僵硬。目前的结果表明：（1）NMDA受体拮抗剂对帕金森样肌肉僵硬的抑制作用至少部分取决于它们对吻侧纹状体的作用；（2）中间-尾侧纹状体中NMDA受体的阻断可能会降低这些化合物的有益作用。
