Vagus nerve stimulation rescues impaired fear extinction and social interaction in a rat model of autism spectrum disorder.

Clinical diagnosis of anxiety disorders is highly prevalent in autism spectrum disorders (ASD). Available treatments for anxiety offer limited efficacy in the ASD population. Vagus nerve stimulation (VNS) has an anxiolytic effect in rats and, when coupled with fear extinction training, VNS enhances extinction of fear in healthy rats. The valproic acid (VPA)-induced rat model of autism shows impaired extinction of fear and deficits in social interaction. This study was designed to test the potential of VNS to rescue extinction learning and influence social behaviors in VPA-exposed rats. After VNS or sham surgery, VPA-exposed rats or controls were subjected to auditory fear conditioning followed by extinction training paired with VNS or sham stimulation. Another cohort was exposed to a social interaction task paired with VNS or sham stimulation. Time spent freezing was not significantly reduced during retention testing 24 h after extinction training in VPA-exposed rats given sham stimulation (p = .26), but freezing levels were significantly lower during the retention test in saline control and in VPA-VNS rats (p < .05), indicating that VNS reverses extinction deficits in VPA-exposed rats. In addition, social interaction scores were significantly lower in VPA-sham rats (p < .0005), but VPA-VNS rats were not significantly different from saline controls (p = .19), suggesting that VNS also alleviates social interaction deficits in VPA-exposed rats. VNS is approved for use in humans for treatment of epilepsy, depression, and stroke. These findings suggest that VNS may be a useful tool for overcoming treatment resistant anxiety in ASD.