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

在帕金森病实验动物模型中，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)处理的大鼠是比较合适的帕金森病模型。在两次注射6-OHDA的大鼠中，去甲肾上腺素浓度在几乎所有脑区都显著降低，表明该动物模型是帕金森病粘附期的最佳动物模型。在动物模型中，D-2多巴胺受体浓度显著升高，但经L多巴治疗后恢复到正常水平。而纹状体M胆碱能受体(Mcr)浓度显著降低，但经L多巴后恢复至正常水平。这些结果表明黑质纹状体的多巴胺能功能强烈地调节纹状体的MCR。P物质、八肽缩胆囊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，MPTP小鼠慢性期纹状体生长抑素水平显著下降。模型动物生长抑素受体结合量增加，但经L多巴治疗后未见恢复。这些结果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，神经肽系统的改变是由于多巴胺能系统功能障碍引起的。帕金森病的实验动物模型有望为帕金森病的生化病理生理学研究、新药开发和减少副作用的治疗方案的研究提供有价值的参考。

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.