Although vitamin A has been reported to be essential to brain homeostasis, some central nervous system (CNS)-associated deleterious effects may be induced by vitamin A or by its metabolites. In this work, we investigated the effects of acute and chronic vitamin A supplementation at therapeutic (1,000 or 2,500 IU/kg/day) or excessive (4,500 or 9,000 IU/kg/day) doses on the redox state of the rat striatum. We found a 1.8- to 2.7-fold increase of lipid peroxidation in the striatum after acute or chronic supplementation (TBARS method). Therapeutic doses induced a 1.6- to 2.2-fold increase of protein carbonylation (dinitrophenylhydrazine (DNPH) derivatization). Vitamin A supplementation induced a 1.2- to 1.4-fold decrease of protein thiol content acutely and chronically. Superoxide dismutase (SOD) activity, assessed through the inhibition of epinephrine's autoxidation, was increased in a dose-dependent manner chronically. Acutely, both therapeutic and excessive vitamin A doses induced a 1.8- to 2.2-fold decrease of catalase (CAT) activity, as determined through the rate of decrease of hydrogen peroxide (H(2)O(2)). Glutathione peroxidase (GPx) activity did not change in this experimental model. Some vitamin A doses decreased the non-protein thiol content only chronically. Vitamin A supplementation decreased the striatal non-enzymatic antioxidant defenses (TRAP assay). Furthermore, our results show that vitamin A supplementation impaired the SOD/CAT ratio. Moreover, we observed a 1.6- to 2.0-fold decrease of locomotion and exploration in an open field after vitamin A supplementation. Therefore, our results suggest that vitamin A supplementation induces oxidative stress in the rat striatum and that it may be related to a metabolic impairment in such brain area.