Melatonin increases striatal dopaminergic function in 6-OHDA-lesioned rats

THE purpose of this study was to assess the in vivo effects of melatonin, a s an antioxidant, on striatal dopaminergic function in rats with a unilater al 6-hydroxydopamine (6-OHDA) lesion of the striatum. Compared with sham-op erated controls and expressed as a ratio relative to the contralateral side , there was an increase in the lipid peroxidation product malondialdehyde ( MDA, 142%) and a significant reduction in tyrosine hydroxylase (TH) enzyme activity (28%) and dopamine (DA, 32%) and its metabolite dihydroxyphenylace tic acid (DOPAC, 50%) 2 weeks after 6-OHDA injection. Melatonin treatment a lmost completely restored MDA levels to normal, suggesting the in vivo acti on of melatonin as an antioxidant. In parallel, partial, but statistically significant recovery of striatal dopaminergic function, including TH enzyme activity and DA levels, also occurred following melatonin treatment. Taken together with our previous reports showing behavioral and histochemical ef fects of melatonin on the nigrostriatal dopaminergic system, the present re sults strongly support the hypothesis that melatonin, as an antioxidant, ma y have beneficial effects on therapeutic approaches for the treatment of ox idative stress-induced neurodegenerative disease such as Parkinson's diseas e (PD). (C) 1998 Lippincott Williams & Wilkins.