Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with increased prevalence
and incidence in recent decades. Its etiology remains largely unclear, but it seems to involve a
strong genetic component and environmental factors that, in turn, induce epigenetic changes during
embryonic and postnatal brain development. In recent decades, clinical studies have shown that inutero
exposure to valproic acid (VPA), a commonly prescribed antiepileptic drug, is an environmental
factor associated with an increased risk of ASD. Subsequently, prenatal VPA exposure in rodents has
been established as a reliable translational model to study the pathophysiology of ASD, which has
helped demonstrate neurobiological changes in rodents, non-human primates, and brain organoids
from human pluripotent stem cells. This evidence supports the notion that prenatal VPA exposure is a
valid and current model to replicate an idiopathic ASD-like disorder in experimental animals. This review
summarizes and describes the current features reported with this animal model of autism and the
main neurobiological findings and correlates that help elucidate the pathophysiology of ASD. Finally,
we discuss the general framework of the VPA model in comparison to other environmental and genetic
ASD models.