Many individuals with autism spectrum disorders (ASD) show both reduced sociability (reduced tendency to seek social interaction), and disabling anxiety symptoms, but the biological relationship between sociability and anxiety is not well understood. Mouse model systems are useful for experimentally testing the relationship between sociability and anxiety. Relative to C57BL/6J mice, BALB/cJ mice show certain behavioral endophenotypes relevant to ASD, including low levels of sociability and high levels of anxiety-related behaviors in non-social tests.
We hypothesized that the low sociability of BALB/cJ mice is related to their generalized high level of anxiety, and that pharmacologically reducing anxiety in BALB/cJ mice would increase their level of social interaction.
To test this hypothesis, we treated BALB/cJ mice with the anxiolytic chlordiazepoxide (CDP), and then measured levels of sociability in a social choice test and anxiety-related behaviors in a non-social paradigm, the elevated zero maze.
Contrary to our original hypothesis, we found that treatment with an anxiolytic medication, CDP (a benzodiazepine), reduces anxiety-related behavior in a nonsocial task, but also significantly decreases sociability. In contrast, treatment with a GABA inverse agonist, beta-carboline does not affect sociability or anxiety.
These findings indicate that decreasing generalized anxiety does not increase sociability in this model system, suggesting that sociability and nonsocial anxiety-related behaviors are subserved by distinct neural circuitry. Future studies will use this mouse model system to further elucidate the neural circuitry and mechanisms that subserve sociability vs. nonsocial anxiety-related behaviors. These mechanistic studies may provide new pharmacologic targets for treating social withdrawal and/or anxiety symptoms in ASD.