Pre- and Postnatal Valproate Exposure Affects Brain Development.

Abstract

This review investigates the teratogenic impact of valproic acid (VPA) on brain development, focusing on dose-dependent and timing-related behavioural and neurological outcomes in rats and mice, with an emphasis on using it as a model for autism spectrum disorders (ASD). Single and multiple administration methods (e.g., oral gavage and intraperitoneal injections) across various rat and mouse strains consistently report behavioural alterations (i.e., altered social interaction and locomotor activity) and neuronal changes, particularly in the hippocampus and cerebellum. We underscore the importance of understanding dose-related changes and the critical role of VPA exposure in determining the long-term neurodevelopmental effects. While animal models provide valuable insights into the pre- and postnatal effects of drug exposure, this chapter also addresses the limitation of extrapolating such findings to humans given the face and construct validity of the model. Overall, this review emphasises VPA's utility in modelling ASD-like behaviours and the need for ongoing research to refine these models for better applicability to humans.