Sex difference in cognitive behavioral alterations and barrel cortex neuronal responses in rats exposed prenatally to valproic acid under continuous environmental enrichment

Autism spectrum disorder is a developmental disorder that can affect social interactions and sensory-motor behaviors. The present study investigates the effect of environmental enrichment (EE) on behavioral alterations and neuron responses associated with the barrel cortex of young adult female and male rats exposed prenatally to valproic acid (VPA). Pregnant female rats were pretreated with either saline or VPA (500 mg/kg, IP) on day 12.5 of gestation. Male and female pups were exposed to either EE or standard-setting (non-enrichment) conditions for 1 month (between postnatal day [PND] 30 and 63-65) and were divided into non-EE (control), EE, VPA, and VPA + EE groups. Three-chamber sociability and social novelty, acoustic startle reflex, and texture discrimination tests were conducted on PND 62. Responses of barrel cortex neurons of male pups were evaluated using the extracellular single-unit recording technique on PND 63-65. Results showed that the performance of rats of both sexes in social interactions, texture discrimination tasks, and acoustic startle reflex significantly decreased in the VPA groups compared with the control rats (P < 0.05). In this regard, EE attenuated the altered deficit performance observed in the VPA animals compared with the VPA-EE animals (P < 0.05). The performance of females was better than males in the discrimination tasks and acoustic startle reflex. In contrast, males were better than females in the three-chamber social interaction test. Additionally, the excitatory receptive field response magnitude of the barrel cortex neurons in the VPA + EE group increased compared with the VPA group (P < 0.05). The results suggest that continuous EE can attenuate cognitive function disturbances in autistic-like rats and, at least at the behavioral level, the effects depend on sex.