Role of Oxytocin in Moderating Autistic-Like Behaviors and Hippocampal Plasticity in Maternal Separated Rats

Autism spectrum disorder (ASD) is the complex neurodevelopmental disorder. It is assumed that maternal separated rat model could be an appropriate environmental-based animal model for ASD to identify promising therapeutic for ASD. In terms of treatment, no specific medication for the core symptoms of ASD has been established. Oxytocin has been suggested as the potential therapeutic agent for the social behavior deficits. While, several issues regarding doses, onset of treatment, route and duration of treatment remain unclear. The main objective of this study was to investigate the effect of maternal separation on the induction of autism-like behaviors in male rats and to examine the therapeutic effect of oxytocin on the behavioral symptoms and associated hippocampal structural plasticity. Method During the first 2 postnatal weeks, pups were separated from mother 3 hours per day. After weaning, rats were treated with oxytocin at a dose of 1 mg/kg (intraperitoneal) for 10 days. In adolescence age, social interaction and stereotypic behaviors were tested with three-chamber and marble-burying tests respectively, and the volume of the hippocampus and its sub-regions were investigated doing the 3-D quantification by applying Cavalieri estimator method using newCAST software. Results Maternal separation induced autistic-like behaviors (p<0.05) (Fig.1) associated with bigger volume of the hippocampus (p<0.05) (Fig.2).And oxytocin contributed to the improvement of the behavioral deficits but not to the modification of the hippocampal volume.Conclusions Findings of the current study showed that early life maternal separation impacts social and stereotype behaviors associated with increasing the hippocampus volume. And the oxytocin could act as a potential therapeutic agent for the autistic-like symptoms with no significant modulatory effect on the volume of the hippocampus.