Time-dependent effects of levodopa on regional brain dopamine metabolism and lipid peroxidation

Levodopa treatment in Parkinson's disease has been suggested to contribute to disease progression through free radical generation. We compared the tim e course of levodopa-induced dopamine metabolism, and the resulting oxidati ve stress, between rat brain regions with varying dopaminergic innervation. At 1,4, 8, and 12 h after levodopa administration (100 mg/kg), dopamine, d ihydroxyphenylacetic acid, and homovanillic acid were measured in striatum and ventral midbrain, regions containing marked dopaminergic innervation, a nd in prefrontal cortex and cerebellum, which possess little dopaminergic i nnervation, Malondialdehyde, a marker of oxidative stress, was measured in additional animals. The return of dopamine and its metabolites to control c oncentrations tended to be slower (by 3-8 h) in cerebellum and prefrontal c ortex than in dopaminergic regions. Malondialdehyde concentrations were dec reased (p < 0.05) in ventral midbrain 8 h posttreatment, but increased in c erebellum 12 h posttreatment. We concluded that levodopa increases dopamine metabolism in nondopaminergic as well as dopaminergic regions, with delaye d clearance of dopamine and its metabolites in nondopaminergic regions, The slower return of dopamine to control levels in nondopaminergic regions may be relevant to some of the side effects of levodopa, No support was found for the hypothesis that levodopa treatment induces oxidative stress, (C) 19 99 Elsevier Science Inc.