Background: Autism spectrum is a type of developmental-neurodegenerative disease commonly reflected in social communications and associated with oxidative stress in the brain. Vitamins D and E, as strong antioxidants, may improve autistic-like behavioral disorders. Objectives: The aim of this study was to determine the effects of vitamins D and E on pain, threshold, motor coordination, and anxiety behavior, as well as oxidative stress parameters in an autistic model in rats. Methods: We induced an experimental model of congenital autism in the rat by injection of valproic acid (500 mg/kg) into pregnant rats on the day 12.5th of gestation. From postnatal day 30 to 60, male offspring received daily injections of vitamins D (5 µg/kg) and/or E (10 mg/kg) or vehicle. Next, their anxiety levels were assessed with the elevated plus maze and open field, pain thresholds with hot plate, motor and balance with rotarod, and spatial learning and memory with T-maze. The rat brain was then removed to measure oxidative markers, including Malondialdehyde, Glutathione, and Catalase. Results: Results indicated that injection of valproic acid-induced autistic-like behaviors, including increased pain threshold, increased anxiety, decreased exploring behaviors, reduced balance power, and motor learning, and produced oxidative stress. Administration of vitamins D and E significantly ameliorated these symptoms. Conclusions: These findings may indicate that vitamins D and E improved sensory, motor, anxiety, and cognitive deficits in an experimental model of autism, probably by reducing the oxidative stress and inflammatory process or maintaining balance in the neurotransmitter system.

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