Effects of prenatal exposure to valproic acid or poly(I:C) on ultrasonic vocalizations in rat pups: The role of social cues

Sociocommunicative deficits commonly observed in autism spectrum disorder (ASD) can be experimentally modeled using rodents' ultrasonic vocalizations (USVs). For example, USVs emitted by pups, separated from their mothers and nest, serve as a useful tool to identify autistic-like behaviors during the early period of development. Being sensitive to social context, these neonatal calls may help to reveal reduced social attachment or abnormal processing of social information. The aim of the present study was to characterize quantitative and structural changes in USVs emitted during isolation by male and female rat pups prenatally exposed to either valproic acid (VPA) or poly(I:C). To determine whether those pups differed from controls in sensitivity to social stimuli, isolation-induced USVs were recorded under two bedding conditions, i.e., novel bedding and soiled bedding from their home cages. Our results demonstrated early communication deficits in both models of autism. We reported a reduced number of USVs emitted by both VPA- and poly(I:C)-exposed males and females. Moreover, compared to the controls, VPA (but not poly(I:C)) pups emitted shorter calls with a higher peak frequency. While VPA offspring demonstrated fewer USVs on the "safe" bedding imbued with maternal/nest odors, this calming effect was not observed in poly(I:C) males, suggesting a more specific deficit in social communication. The present results demonstrate that qualitative along with quantitative analyses of neonatal vocalizations are a useful tool for assessing early sociocommunicative deficits in ASD models. Notably, more specific changes in USV emission may be detected when introducing social context.