The GABAB receptor agonist STX209 reverses the autism-like behaviour in an animal model of autism induced by prenatal exposure to valproic acid

Abstract

autism spectrum disorder (aSd) is a lifelong neuro- developmental condition characterized by impaired social interaction, compromised communication, and restrictive or stereotyped behaviours and interests. due to the complex pathophysiology of aSd, there are currently no available medical therapies for improving the associated social defi- cits. consequently, the present study investigated the effects of STX209, a selective γ-aminobutyric acid type B receptor (GaBaBr2) agonist, on an environmental rodent model of autism. The mouse model of autism induced by prenatal expo- sure to valproic acid (VPa) was used to assess the therapeutic potential of STX209 on autism-like behaviour in the present study. This study investigated the effects of STX209 on VPa model mice via behavioral testing and revealed a significant reversal of core/associated autism-like behavior, including sociability and preference for social novelty, novelty recogni- tion, locomotion and exploration activity and marble-burying deficit. This may be associated with STX209 correcting dendritic arborization, spine density and GaBaBr2 expression in hippocampus of VPa model mice. However, expression of glutamic acid decarboxylase 65/67 in the hippocampus were not altered by STX209. The present results demonstrated that STX209 administration ameliorated autism-like symptoms in mice exposed to VPa prenatally, suggesting that autism-like symptoms in children with a history of prenatal VPa exposure may also benefit from treatment with the GABABR2 agonist STX209.