Ameliorating age-dependent effects of resveratrol on VPA-induced social impairments and anxiety-like behaviors in a rat model of neurodevelopmental disorder

Although anxiety disorders, as well as difficulties in social interaction, are documented in children with autism spectrum disorder (ASD) as a neurodevelopmental disorder, the effectiveness of potential therapeutic procedures considering age and sex differences is under serious discussion. The present study aimed to investigate the effect of resveratrol (RSV) on anxiety-like behaviors and social interaction in juvenile and adult rats of both sex in a valproic acid (VPA)-induced autistic-like model. Prenatal exposure to VPA was associated with increased anxiety, also causing a significant reduction in social interaction in juvenile male subjects. Further administration of RSV attenuated VPA-induced anxiety symptoms in both sexes of adult animals and significantly increased the sociability index in male and female juvenile rats. Taken together, it can be concluded that treatment with RSV can attenuate some of the harsh effects of VPA. This treatment was especially effective on anxiety-like traits in adult subjects of both sexes regarding their performance in open field and EPM. We encourage future research to consider the sex and age-specific mechanisms behind the RSV treatment in the prenatal VPA model of autism.