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 acute footshock stress, using analogous parameters to those commonly used in fear conditioning assays, on the sociability of male and female C57BL/6J mice in a standard social approach test. Animals were divided into two main groups of footshock stress (22 male, 24 female) and context exposed control (23 male and 22 female). Each group had mice that were treated intraperitoneally with either the benzodiazepine—alprazolam (control: 10 male, 10 female; stress: 11 male, 11 female), or vehicle (control: 13 male, 12 female; stress: 11 male, 13 female). In all groups, neuronal activation during social approach 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 stimulus, it did increase defensive tail-rattling behavior specifically in males (p = 0.0022). This stress-induced increase in tail-rattling was alleviated by alprazolam (p = 0.03), yet alprazolam had no effect on female tail-rattling behavior in the stress group. Alprazolam lowered cFos expression in the medial prefrontal cortex (p = 0.001 infralimbic area, p = 0.02 prelimbic area), and social approach induced sex-dependent differences in cFos activation in the ventromedial intercalated cell clusters (p = 0.04). Social approach following stress-induced cFos expression was positively correlated with latency to approach and negatively correlated with sociability in the prelimbic area and multiple amygdala subregions (all p < 0.05). Collectively, our results suggest that acute footshock stress induces sex-dependent alterations in defensiveness and differential patterns of cFos activation during social approach.

Contributions of associative and non-associative learning to the dynamics of defensive ethograms

“…Within the UN and SO control groups, we observed a higher degree of tail rattling responses to the SCS during extinction compared to the PA group, and tail rattling was more prominent during the tone period. Tail rattling has been observed in mice when determining hierarchical relationships (Haber and Simmel 1976, Terranova et al, 1998, Dorofeikova et al, 2023, anticipating fighting (Miczek et al, 2001), and encountering looming threat (Salay et al, 2018). Thus, tail rattling may be a behavior elicited in stressed mice that anticipate an uncertain threat.…”

Effects of uniform rocking exercise on anxiety and its related nuclei in acutely stressed rats

“…However, rocking did not alleviate the decrease in mPFC neuronal activity but rather exacerbated it, suggesting that rocking may not produce anxiolytic effects by decreasing mPFC glutamatergic neuronal activity. However, it has also been reported that the administration of benzodiazepines to rats stimulated by plantar electroshock was able to reduce C-fos expression in the mPFC [37]. So further evidence is needed on what type of neurons these reduced activities are.…”