Chronic stress represents a vulnerability factor for anxiety and depressive disorders and has been widely used to model aspects of these disorders in rodents. Disinhibition of somatostatin (SST)-positive GABAergic interneurons in mice by deletion of γ2 GABA_A receptors selectively from these cells (SSTCre:γ2^f/f mice) has been shown to result in behavioral and biochemical changes that mimic the responses to antidepressant doses of ketamine. Here we explored the extent to which SSTCre:γ2^f/f mice exhibit resilience to unpredictable chronic mild stress (UCMS). We found that male SSTCre:γ2^f/f mice are resilient to UCMS-induced (i) reductions in weight gain, (ii) reductions in SST-immuno-positive cells in medial prefrontal cortex (mPFC), (iii) increases in phosphorylation of eukaryotic elongation factor 2 (eEF2) in mPFC, and (iv) increased anxiety in a novelty suppressed feeding test. Female SSTCre:γ2^f/f mice were resilient to UCMS-induced reductions in SST-immuno-positive cells indistinguishably from males. However, in contrast to males, they showed no UCMS effects on weight gain independent of genotype. Moreover, in mPFC of female γ2^f/f control mice, UCMS resulted in paradoxically reduced p-EF2 levels without stress effects in the SSTCre:γ2^f/f mutants. Lastly, female SSTCre:γ2^f/f mice showed increased rather than reduced UCMS induced anxiety compared to γ2^f/f controls. Thus, disinhibition of SST interneurons results in behavioral resilience to UCMS selectively in male mice, along with cellular resilience of SST neurons to UCMS independent of sex. Thus, mechanisms underlying vulnerability and resilience to stress are sex specific and map to mPFC rather than hippocampus but appear unrelated to changes in expression of SST as a marker of corresponding interneurons.

慢性应激代表了焦虑和抑郁症的脆弱性因素，已被广泛用于在啮齿类动物中模拟这些疾病的各个方面。通过选择性地从这些细胞（SSTCre：γ2f ^{/ f}小鼠）中删除γ2GABA _A受体来抑制小鼠中生长抑素（SST）阳性GABA能中间神经元的行为和生化变化可模拟对抗抑郁药剂量的反应。氯胺酮。在这里，我们探讨了SSTCre：γ2f ^{/ f}小鼠对不可预测的慢性轻度应激（UCMS）的抵抗力的程度。我们发现男性SSTCre：γ2f ^{/ f}小鼠对UCMS诱导的（i）体重增加减少，（ii）内侧前额叶皮层（mPFC）中SST免疫阳性细胞减少，（iii）mPFC中的真核延伸因子2（eEF2）磷酸化增强具有恢复力，以及（iv）在新奇抑制的喂食测试中焦虑加剧。雌性SSTCre：γ2f ^{/ f}小鼠对UCMS诱导的SST免疫阳性细胞减少与雄性没有区别。但是，与雄性相反，它们对基因型无影响，没有UCMS对体重增加的影响。此外，在雌性γ2f ^{/ f}对照小鼠的mPFC中，UCMS导致p-EF2水平自相矛盾地降低，而在SSTCre：γ2f ^{/ f}突变体中没有应激效应。最后，女性SSTCre：γ2f ^{/ f}与γ2f ^{/ f}对照相比，小鼠显示出UCMS诱发的焦虑增加而不是减少。因此，SST间神经元的抑制作用导致雄性小鼠选择性地对UCMS表现出行为适应力，以及SST神经元对UCMS的细胞适应能力与性别无关。因此，潜在的脆弱性和对压力的适应力的机制是性别特异性的，并映射到mPFC而不是海马，但似乎与作为相应中间神经元标志物的SST表达变化无关。