Effects of footshock stress on social behavior and neuronal activation in the medial prefrontal cortex and amygdala of male and female mice

Abstract

Social behavior is complex and fundamental, and its deficits are common pathological features for several psychiatric disorders including anxiety, depression, and posttraumatic stress disorder. Acute stress may have a negative impact on social behavior, and these effects can vary based on sex. The aim of this study was to explore the effect of two days of footshock stress on the sociability of male and female C57Bl/6J mice measured using a standard social interaction test. Animals were divided into two main groups of footshock exposure or context exposure control. Each group had mice that were treated with either the benzodiazepine alprazolam, or vehicle. In all groups, neuronal activation during social interaction was assessed using immunohistochemistry against the immediate early gene product cFos. Although footshock stress did not significantly alter sociability or latency to approach a social interaction counterpart, it did increase defensive tail-rattling behavior specifically in males. This stress-induced increase in tail-rattling was alleviated by alprazolam, yet alprazolam had no effect on female tail-rattling behavior in the stress group. Alprazolam lowered cFos expression in the medial prefrontal cortex, and social interaction induced sex-dependent differences in cFos activation in the ventromedial intercalated cell clusters. Overall, our results suggest that acute footshock stress induces sex-dependent alterations in defensiveness and patterns of cFos activation during social interaction tests.