Abstract: The effect of melatonin (1 mg/kg BW i.p./day) on the oxidative changes produced by 3-nitropropionic acid (20 mg/kg BW/day for 4 days) in rat striatal and cortical synaptosomes was investigated. The effects of 3-nitropropionic acid were evaluated as changes in the quantity of lipid peroxidation products, protein carbonyl groups and superoxide dismutase and succinate dehydrogenase activities. 3-Nitropropionic acid caused a rise in lipid peroxidation levels and protein carbonyls content whereas it induced a reduction in the activity of succinate dehydrogenase and triggered an enhancement in superoxide dismutase activity. These changes were prevented by previous administration of melatonin. Our results reveal: (i) 3-nitropropionic acid induces a status of oxidative stress in some brain regions of the Wistar rat; (ii) melatonin prevents the deleterious effects induced by the acid. In conclusion, the results show the ability of melatonin to modify the neural response to 3-nitropropionic acid with the protective mechanism likely involving the antioxidative processes of melatonin.