Adolescent female valproic acid rats have impaired extra-dimensional shifts of attention and enlarged anterior cingulate cortices

Abstract

In order to develop better treatments for autism spectrum disorder (ASD) it is critical to understand the developmental trajectory of the disorder and the accompanying brain changes. This study used the valproic acid (VPA) model to induce ASD-like symptoms in rodents. Prior studies have demonstrated that VPA animals are impaired on executive function tasks, paralleling results in humans with ASD. Here, VPA adolescent female rats were impaired on a set-shifting task and had enlarged frontal cortices compared to control females. The deficits observed in the VPA female rats mirrors results in females with ASD. In addition, adolescent VPA females with enlarged frontal cortices performed the worst across the entire task. These brain changes in adolescence are also found in adolescent humans with ASD. These novel findings highlight the importance of studying the brain at different developmental stages.

Keywords: ASD; Brain volume; Cognitive flexibility; Set-shifting; VPA.