Behavioral and molecular changes in the mouse in response to prenatal exposure to the anti-epileptic drug valproic acid

F. I. Roullet, L. Wollaston, D. deCatanzaro, J. A. Foster

Research output: Contribution to journalArticlepeer-review

143 Scopus citations

Abstract

Experiments in rodents have indicated that maternal valproic acid (VPA) exposure has permanent adverse effects upon neurological and behavioral development. In humans, prenatal exposure to VPA can induce fetal valproate syndrome, which has been associated with autism. The present study examined mouse pups exposed in utero to VPA, measuring physical development, olfactory discrimination, and social behavior as well as expression of plasticity-related genes, brain derived neurotrophic factor (BDNF) and NMDA receptor subunits NR2A and NR2B. VPA-exposed mice showed delayed physical development, impaired olfactory discrimination, and dysfunctional pre-weaning social behavior. In situ hybridization experiments revealed lower cortical expression of BDNF mRNA in VPA animals. These results support the validity of the VPA mouse model for human autism and suggest that alterations in plasticity-related genes may contribute to the behavioral phenotype.

Original languageEnglish (US)
Pages (from-to)514-522
Number of pages9
JournalNeuroscience
Volume170
Issue number2
DOIs
StatePublished - Oct 13 2010
Externally publishedYes

Keywords

  • Brain derived neurotrophic factor
  • Gene expression
  • In situ hybridization
  • Social behavior
  • Valproic acid

ASJC Scopus subject areas

  • Neuroscience(all)

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