| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1988: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1987: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1986: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Research Abstract |
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.
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