Repeated administration of high dose levodopa enhances hydroxyl radical production in the rat striatum denervated with 6-hydroxydopamine

Abstract

We examined whether levodopa ( l-DOPA) might increase production of hydroxyl radicals in intact and dopamine-denervated rat striatum. Salicylate trapping combined with in vivo microdialysis provided measurements of 2,3-dihydroxybenzoic acid (2,3-DHBA) as a marker of hydroxyl radical production. Acute administration of high-dose l-DOPA (200, 500 mg/kg, i.p.) did not alter 2,3-DHBA levels in intact striatum or in striatum denervated with 6-hydroxydopamine. On the other hand, l-DOPA administration (200 mg/kg, i.p.) transiently increased 2,3-DHBA in dopamine-denervated striatum of rats after repeated administration of l-DOPA (200 mg/kg, i.p., once daily for 16 days). The results indicated that repeated administration of high dose l-DOPA increased production of hydroxyl radicals in dopamine-denervated striatum.