EFFECTS OF ENHANCED STRIATAL DOPAMINE TURNOVER IN-VIVO ON GLUTATHIONEOXIDATION

In Parkinson's disease (PD), a compensatory increase in dopamine (DA) turnover occurs in the remaining nigrostriatal dopaminergic neurons, r esulting in greater exposure of each neuron to hydrogen peroxide (H2O2 ) derived from oxidative deamination of DA. The formation of oxyradica ls from H2O2 is regarded as a mechanism that could contribute to the p rogression of PD, and incubation of rat striatal synaptosomes with lev odopa (LD) results in an increase in oxidized glutathione (GSSG), indi cative of oxidant stress. The present study was undertaken to determin e whether striatal GSSG levels increase in response to administration of LD in vivo. Acute and repeated (3-week) treatment of normal rats wi th LD at doses of up to 100 mg/kg did not increase striatal GSSG despi te marked increase in DA turnover. These results suggest that intact s triatum may possess increased defense capacity against oxidant stress generated by increased DA turnover as compared with isolated synaptoso mes.