Involvement of hydroxy radical stress in neurotoxicity in rat nigrostriatal system

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To examine the involvement of hydroxyl radical stress in neurotoxicity of acute and chronic administration of the dopaminergic agonists, we planed to perform the microdialysis and various kinds of histological studies in a rat model of Parkinson's disease by 6-hydroxydopamine (6-OHDA), and furthermore in the model having received intrastriatal grafts of fetal ventral mesencephalon. With the utilization of the microdialysis and HPLC-ECD, the extracellular concentration of striatal L-DOPA, dopamine, its metabolites, glutamate and GABA, and furthermore the formation of 2,3-dihydroxybenzoic acid (2,3-DHBA), derived from the reaction of hydroxyl radicals and salicylate in perfusion, were monitored and detected following single or repeated administration of L-DOPA or methamphetamine (i.p.). We have examined the topological specificity of L-DOPA- or methamphetamine-induced activation of the immediate-early gene proteins, c-Fos and Zif268 in the nigrostriatal system in the 6-OHDA rat with or without the intrastriatal grafts. We have not yet complete this study, and are continuing further study.