Neonatal Oxytocin Treatment Ameliorates Autistic-Like Behaviors and Oxytocin Deficiency in Valproic Acid-Induced Rat Model of Autism

摘要

Autism spectrum disorder (ASD) is characterized by impaired social communication and repetitive/stereotyped behaviors. The neuropeptide oxytocin (OXT) plays a critical role in regulating social behaviors in the central nervous system, as indicated in both human and animal studies. We hypothesized that central OXT deficit is one of causes of etiology of ASD, which may be responsible for the social impairments. To test our hypothesis, central OXT system was examined in valproic acid (VPA)-induced rat model of autism (VPA rat). Our results showed that adolescent VPA rats exhibited a lower level of OXT mRNA and fewer OXT-ir cells in the hypothalamus than control rats. Additionally, OXT concentration in cerebrospinal fluid (CSF) was reduced. The number of OXT-ir cells in the supraoptic nucleus (SON) of neonatal VPA rats was also lower. Autistic-like behaviors were observed in these animals as well. We found that an acute intranasal administration of exogenous OXT restored the social preference of adolescent VPA rats. Additionally, early postnatal OXT treatment had long-term effects ameliorating the social impairments and repetitive behaviors of VPA rats until adolescence. This was accompanied by an increase in OXT-ir cells. Taken together, we demonstrated there was central OXT deficiency in the VPA-induced rat model of autism, and showed evidence that early postnatal OXT treatment had a long-term therapeutic effect on the autistic-like behaviors in VPA rats.