Kretschmer B D, Winterscheid B, Danysz W, Schmidt W J
Department of Neuropharmacology, University of Tübingen, Federal Republic of Germany.
J Neural Transm Gen Sect. 1994;95(2):123-36. doi: 10.1007/BF01276431.
Catalepsy--a state of postural immobility (akinesia) with muscular rigidity (rigor)--and reduced locomotion in animals are behavioral deficits showing similarities with symptoms of Parkinson's disease (PD). The effects of the glycine site antagonists 7-chlorokynurenate and (R)-HA-966 on haloperidol-(D 2 antagonist) and SCH 23390- (D 1 antagonist) induced catalepsy and reduced locomotion are investigated in rats. Both antagonists dose-dependently counteract dopamine D 2 receptor mediated catalepsy but they have no influence on locomotion. Neither 7-chlorokynurenate nor (R)-HA-966 has any effect on dopamine D 1 receptor mediated catalepsy. This finding is surprising, since NMDA receptor antagonists counteract both, dopamine D 1 and D 2 receptor mediated catalepsy. D 1 and D 2 receptors are located on different populations of neurons. Thus, the present findings suggest that these different neuronal populations have different sensitivity for ligands binding at the glycine binding site of the NMDA receptor.
僵住症——一种伴有肌肉强直(僵硬)的姿势不动(运动不能)状态——以及动物运动减少是与帕金森病(PD)症状相似的行为缺陷。研究了甘氨酸位点拮抗剂7-氯犬尿氨酸和(R)-HA-966对氟哌啶醇(D2拮抗剂)和SCH 23390(D1拮抗剂)诱导的僵住症及运动减少的影响。两种拮抗剂均剂量依赖性地对抗多巴胺D2受体介导的僵住症,但对运动无影响。7-氯犬尿氨酸和(R)-HA-966对多巴胺D1受体介导的僵住症均无任何作用。这一发现令人惊讶,因为NMDA受体拮抗剂能对抗多巴胺D1和D2受体介导的僵住症。D1和D2受体位于不同的神经元群体上。因此,目前的研究结果表明,这些不同的神经元群体对结合于NMDA受体甘氨酸结合位点的配体具有不同的敏感性。