Novel Serotonin Antagonist Improves Social Behavior and is Ineffective in Correcting Repetitive Behavior in a Mouse Model of Autism

CREVELING 6

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restrictive and repetitive behaviors, impaired communication, and reduced social interaction. There is no single mechanism responsible for the manifestation of autism’s symptoms, however it has been linked to several potentially related genes likely interacting with environmental factors. The serotonin (5-HT) system has been implicated as one potential cause of autism’s core symptoms. By targeting the only serotonin receptor found exclusively in the central nervous system, 5-HT₆, we can determine whether this system is contributing to ASD’s symptoms. A novel 5-HT₆ antagonist, BGC 20-761, was tested for its ability to alleviate the autistic-like repetitive and social behaviors of the C58/J inbred mouse strain. An intraperitoneal injection of the antagonist or vehicle control was administered to C58/J and C57BL/6J mice. Following the injection, the mice were tested for social and repetitive behaviors using two different assays. The repetitive behavior assay was conducted by placing the mouse in an empty home cage and the social behavior assay was conducted using a standard three-chamber test. The antagonist significantly increased the sociability of the female C58 mice and there was a significant increase in the female rear and male self-groom durations. This potentially supports the idea that the mice are exhibiting increased social behavior as a result of higher anxiety levels under the antagonist condition. Future work will test the anxiety behavior of the C58 mice after an injection of the antagonist in order to determine whether this could be contributing to our results.