Interactions between Classical Neurotransmitter Systems and Neuropeptide Systems in Experimental Animal Model of Parkinsonism

本实验在帕金森病动物模型上研究了经典神经递质系统和神经肽系统之间的相互作用。结果表明，1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）处理的小鼠、Weaver小鼠和6-OHDA双重（黑质和侧脑室）处理的大鼠是适合帕金森病模型的动物。在双重给予6-OHDA的大鼠中，几乎所有脑区的去甲肾上腺素浓度均显著降低，表明该动物模型是帕金森病晚期的最佳模型。在动物模型中，D-2多巴胺受体浓度显著升高，但在给予L-多巴后恢复至正常水平。另一方面，纹状体毒蕈碱胆碱能受体（MCR）的浓度显着降低，但在给予L-多巴后恢复到正常水平。这些结果表明黑质纹状体的多巴胺能功能对纹状体MCR有很强的调节作用。P物质、八肽胆囊收缩素和生长抑素水平在动物模型的任何脑区均无变化。有趣的是，纹状体生长抑素水平在MPTP小鼠的慢性期显示出显着下降。生长抑素受体结合增加的模型动物，但没有恢复管理的L-多巴。提示帕金森病的核心生化功能障碍是多巴胺能和胆碱能系统的改变，其次是神经肽系统的改变，帕金森病的实验动物模型对研究帕金森病的生化病理生理、新药开发和减轻副作用的治疗方案具有重要价值。

Interactions between classical neurotransmitter systems and neuropeptide systems were studied in experimantal animal model of parkinsonism. It was revealed that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, Weaver mice and 6-OHDA double (substantia nigra and lateral ventricle)-treated rats were suitable model for parkinsonism. In the rats with double administrations of 6-OHDA, the noradrenaline concentration strongly decreased in the almost all brain regions, indicating that this animal model is best model for advernced stage of parkinsonism. In the animal model, the concentration of D-2 dopamine receptor increased significantly but recovered to the normao level after administration of L-dopa. On the other hand, the concentration of the striatal muscarinic cholinergic receptor (MCR) decreased significantly but recovered to the normal level after administration of L-dopa. These findings indicated that the striatal MCR are strongly requlated by the nigrostriatal dopaminergic function. Substance P, cholecystokinin-octapeptide and somatostatin levels showed no change in any brain region of animal models. Interestingly, striatal somatostatin level showed a marked decrease in chronic phase of MPTP mice. Somatostatin receptor binding increased in the model animal, but did not recovered by administration of L-dopa. These data suggest that core biochemical dysfunctions in parkinsonism are changes in dopaminergic and cholinergic systems, and changes in neuropeptide systems are seconderily changes due to dopaminergic dysfunctions.Experimental animal model of parkinsonism is expected to be valuable in the studies on the biochemical pathophysiology of Parkinson's disease, the development of new drugs and studies on the therapeutic regiments to minimize the side effects.