Effect of Sex and Age on Repetitive, Stereotyped, and Exploratory Behaviors in a Rat Model of Valproic Acid-Induced Autism

Abstract

Autism is characterized by behavioral impairments in social interaction, language and communication as well as restricted interests and activities. The present study examined stereotypical repetitive behaviors, anxiety, and locomotor as well as exploratory activities in rat model of valproic acid-induced autism. Materials and Methods: Pregnant Spraque dawley rats were administered by either valproic acid (VPA group, 500 mg/kg, n=10) or saline (control group, n=10) during fetal neural tube development on embryonic day 12.5. All male or female offspring were investigated in this study. Stereotypical and anxietyexploratory behaviors were assessed using Y-maze and open field tests, respectively. Results: A single intra-peritoneal injection of VPA to pregnant rats produced severe autistic-like symptoms in the offspring. The results showed significant behavioral impairments including enhanced stereotyped repetitive behaviors, increased anxiety, and decreased exploratory activities in male rats at postnatal day 30 and 60 compared to female rats. Conclusion: Our data suggest that early embryonic exposure to VPA in rats provides an appropriate model for autism in male offspring.