Whether social contact contributes to the underlying mechanisms of depression and the observed sex differences is unclear. In this study, we subjected young male and female mice to separation- and restraint-induced stress for 4 weeks and assessed behaviors, neurotransmitter levels, hormones, and inflammatory cytokines. Results showed that, compared with controls, male mice exposed to stress displayed significant decreases in body weight and sucrose preference after 1 week. In the fourth week, they exhibited a higher degree of anxiety (open field test) and depressive-like behavior (forced swim test). Moreover, the males showed significant decreases in monoamine neurotransmitters, including norepinephrine and dopamine in striatum, and an increase in pro-inflammatory cytokines, such as tumor necrosis factor α and interleukin 1β in serum. In contrast, females showed persistent loss of weight during stress and displayed significant decreases in sucrose preference after stress. Importantly, the females but not males showed activation of the hypothalamus-pituitary-adrenal (HPA) axis, with significantly higher levels adrenocorticotropic hormone. Additionally, mRNA level of c-fos and AVP showed there was significant interaction between stress and sex. Finally, we conclude that an imbalance of the HPA axis and inflammation might be important contributors to sex differences in separation/restraint-induced depressive behavior and that changes might be mediated by c-fos and AVP.

中文翻译：

---

下丘脑-垂体-肾上腺轴失衡和炎症导致分离和约束诱发的抑郁症的性别差异。

社会交往是否会导致抑郁的潜在机制以及所观察到的性别差异尚不清楚。在这项研究中，我们对雄性和雌性小鼠进行了为期4周的分离和约束诱导应激，并评估了其行为，神经递质水平，激素和炎性细胞因子。结果表明，与对照组相比，暴露于压力下的雄性小鼠在1周后体重和蔗糖偏爱性显着降低。在第四周，他们表现出更高的焦虑程度（开放视野测试）和抑郁样行为（强迫游泳测试）。此外，男性显示纹状体中的去甲肾上腺素和多巴胺的单胺神经递质显着减少，血清中的肿瘤坏死因子α和白介素1β等促炎细胞因子增加。相反，女性在压力下表现出持续的体重减轻，并且在压力后显示出蔗糖偏爱的显着降低。重要的是，女性而不是男性表现出下丘脑-垂体-肾上腺（HPA）轴的激活，其促肾上腺皮质激素水平明显更高。此外，c-fos和AVP的mRNA水平表明，压力和性别之间存在显着的相互作用。最后，我们得出结论，HPA轴和炎症的失衡可能是导致分离/约束引起的抑郁行为中性别差异的重要因素，并且这种变化可能是由c-fos和AVP介导的。女性而非男性表现出下丘脑-垂体-肾上腺（HPA）轴的激活，其促肾上腺皮质激素水平明显升高。此外，c-fos和AVP的mRNA水平表明，压力和性别之间存在显着的相互作用。最后，我们得出结论，HPA轴和炎症的失衡可能是导致分离/约束引起的抑郁行为中性别差异的重要因素，并且这种变化可能是由c-fos和AVP介导的。女性而非男性表现出下丘脑-垂体-肾上腺（HPA）轴的激活，其促肾上腺皮质激素水平明显升高。此外，c-fos和AVP的mRNA水平表明，压力和性别之间存在显着的相互作用。最后，我们得出结论，HPA轴和炎症的失衡可能是导致分离/约束引起的抑郁行为中性别差异的重要因素，并且这种变化可能是由c-fos和AVP介导的。