Department of Psychology, Tulane University, New Orleans, LA, United States of America.
Tulane Brain Institute, Tulane University, New Orleans, LA, United States of America.
PLoS One. 2023 Feb 9;18(2):e0281388. doi: 10.1371/journal.pone.0281388. eCollection 2023.
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.
社会行为复杂而基础，其缺陷是包括焦虑、抑郁和创伤后应激障碍在内的几种精神疾病的常见病理特征。急性应激可能对社会行为产生负面影响，并且这些影响可能因性别而异。本研究旨在探索类似于常用于恐惧条件反射测定的参数的急性足底电击应激对标准社会接近测试中雄性和雌性 C57BL/6J 小鼠社交能力的影响。动物分为足底电击应激的两个主要组（22 只雄性，24 只雌性）和对照（23 只雄性和 22 只雌性）。每个组都有接受苯二氮䓬-阿普唑仑（对照组：10 只雄性，10 只雌性；应激组：11 只雄性，11 只雌性）或载体（对照组：13 只雄性，12 只雌性；应激组：11 只雄性，13 只雌性）处理的小鼠。在所有组中，通过针对即时早期基因产物 cFos 的免疫组织化学评估社会接近期间的神经元激活。尽管足底电击应激并未显著改变社交能力或接近社交刺激的潜伏期，但它确实特异性地增加了雄性的防御性甩尾行为（p = 0.0022）。这种应激诱导的甩尾增加被阿普唑仑缓解（p = 0.03），但阿普唑仑对应激组中雌性的甩尾行为没有影响。阿普唑仑降低了内侧前额叶皮质（p = 0.001 内嗅区，p = 0.02 前扣带回区）中的 cFos 表达，并且社会接近诱导了腹内侧中间细胞簇中性别依赖的 cFos 激活的差异（p = 0.04）。应激诱导的 cFos 表达后的社会接近与前扣带回区和多个杏仁核亚区的接近潜伏期呈正相关，与社交能力呈负相关（所有 p < 0.05）。总的来说，我们的结果表明，急性足底电击应激诱导了性别依赖性的防御性改变，并在社会接近期间诱导了不同的 cFos 激活模式。
