The adverse effects of stress on brain and behavior have long been known and well-studied, with abundant evidence linking stress to, among other things, mood and anxiety disorders. Likewise, many have investigated potential treatments for stress-related mood and anxiety phenotypes and demonstrated good response to standard antidepressant medications like selective serotonin reuptake inhibitors (SSRIs), as well as environmental manipulations like exercise or enrichment. However, the extent to which stress and various treatments act on overlapping pathways in the brain is less well understood. Here, we used a widely studied social defeat stress paradigm to induce a robust depression- and anxiety-like phenotype and chronic corticosterone elevation that persisted for at least 4 weeks in wild type male mice. When mice were treated with either the SSRI fluoxetine or an enriched environment, both led to similar behavioral recovery from social defeat. We then focused on the amygdala and assessed the effects of social defeat, fluoxetine, and enrichment on 168 genes broadly related to synaptic plasticity or oxidative stress. We found 24 differentially expressed genes in response to social defeat stress. Interestingly, fluoxetine led to broad normalization of the stress-induced expression pattern while enrichment led to expression changes in a separate set of genes. Together, this study provides additional insight into the chronic effects of social defeat stress on behavior and gene expression in the amygdala. The findings also suggest that, for a subset of genes assessed, fluoxetine and environmental enrichment have strikingly divergent effects on expression in the amygdala, despite leading to similar behavioral outcomes.

压力对大脑和行为的不利影响早已为人所知并得到充分研究，有大量证据表明压力与情绪和焦虑症等因素有关。同样，许多人研究了与压力相关的情绪和焦虑表型的潜在治疗方法，并证明对选择性 5-羟色胺再摄取抑制剂 (SSRIs) 等标准抗抑郁药物以及运动或丰富环境等环境控制有良好的反应。然而，人们对压力和各种治疗作用于大脑中重叠通路的程度知之甚少。在这里，我们使用广泛研究的社交失败压力范式来诱导强烈的抑郁和焦虑样表型和慢性皮质酮升高，这种情况在野生型雄性小鼠中持续至少 4 周。当小鼠接受 SSRI 氟西汀或丰富的环境治疗时，两者都会导致类似的行为从社交失败中恢复。然后我们专注于杏仁核并评估社交失败、氟西汀和富集对与突触可塑性或氧化应激广泛相关的 168 个基因的影响。我们发现了 24 个差异表达的基因来应对社交失败压力。有趣的是，氟西汀导致应激诱导的表达模式广泛正常化，而富集导致一组单独基因的表达变化。总之，这项研究提供了对社交失败压力对杏仁核行为和基因表达的慢性影响的更多见解。研究结果还表明，对于评估的一部分基因，