The valproic acid-induced rodent model of autism

Exp Neurol. 2018 Jan;299(Pt A):217-227. doi: 10.1016/j.expneurol.2017.04.017. Epub 2017 May 2.


Autism is a lifelong neurodevelopmental disorder characterized by impairments in social communication and interaction and by repetitive patterns of behavior, interests and activities. While autism has a strong genetic component, environmental factors including toxins, pesticides, infection and drugs are known to confer autism susceptibility, likely by inducing epigenetic changes. In particular, exposure to valproic acid (VPA) during pregnancy has been demonstrated to increase the risk of autism in children. Furthermore, rodents prenatally exposed to this drug display behavioral phenotypes characteristics of the human condition. Indeed, in utero exposure of rodents to VPA represents a robust model of autism exhibiting face, construct and predictive validity. This model might better represent the many cases of idiopathic autism which are of environmental/epigenetic origins than do transgenic models carrying mutations in single autism-associated genes. The VPA model provides a valuable tool to investigate the neurobiology underlying autistic behavior and to screen for novel therapeutics. Here we review the VPA-induced rodent model of autism, highlighting its importance and reliability as an environmentally-induced animal model of autism.

Keywords: Anxiety; Connectivity; Environmental insult; HDAC inhibitor; Histone deacetylase; In utero exposure; Molecular changes; Repetitive behavior; Sociability; Spines; Valproate.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Autism Spectrum Disorder / chemically induced*
  • Autism Spectrum Disorder / psychology
  • Behavior, Animal / drug effects
  • Disease Models, Animal
  • Female
  • Humans
  • Mice
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Rats
  • Social Behavior
  • Teratogens*
  • Valproic Acid*


  • Teratogens
  • Valproic Acid