Social instability is an effective chronic stress paradigm for both male and female mice.
Social instability is an effective chronic stress paradigm for both male and female mice.
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对于雄性和雌性小鼠来说，社会不稳定是一种有效的慢性压力范例。
DOI：
10.1016/j.neuropharm.2019.107780
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发表时间：
2019
影响因子：
4.7
通讯作者：
Samuels,BenjaminA
中科院分区：
文献类型：
--
作者：
Yohn,ChristineN;Ashamalla,SandraA;Bokka,Leshya;Gergues,MarkM;Garino,Alexander;Samuels,BenjaminA
尽管与压力相关的疾病在女性中的发病率较高，但临床前研究主要集中在男性。慢性压力范式，例如慢性社交失败和慢性皮质酮 (CORT) 管理，主要在男性中设计和验证，随后在女性中使用这些范式的尝试表明，行为和 HPA 轴对压力的反应存在性别差异。在这里，我们评估了对长期 CORT 暴露的行为反应，并开发了一种社会压力范式，即社会不稳定压力 (SIS)，该范式将成年小鼠每 3 天暴露于不稳定的社会等级制度，持续 7 周。对慢性 CORT 的反应出现了性别差异，在 CORT 治疗的男性而非女性中诱导了负价行为。 SIS 在开放场、光暗和新奇抑制进食测试中有效诱导负价行为，增加强迫游泳测试中的不动性，并激活雄性和雌性的下丘脑-垂体-肾上腺 (HPA) 轴。重要的是，虽然发情周期对行为有影响，但这种变异性并不影响 SIS 对行为的总体影响，这表明在使用 SIS 时不需要跟踪发情。此外，在男性和女性中使用氟西汀（FLX）长期抗抑郁治疗后，SIS 对负价行为的影响也被逆转。 SIS 还减少了雌性小鼠的成年海马神经发生，而长期 FLX 治疗则增加了雄性和雌性小鼠的成年海马神经发生。总体而言，这些数据表明 SIS 范式是一种行为学上有效的方法，可以有效诱导成年雄性和成年雌性小鼠的慢性应激。
Despite stress-associated disorders having a higher incidence rate in females, preclinical research mainly focuses on males. Chronic stress paradigms, such as chronic social defeat and chronic corticosterone (CORT) administration, were mainly designed and validated in males and subsequent attempts to use these paradigms in females has demonstrated sex differences in the behavioral and HPA axis response to stress. Here, we assessed the behavioral response to chronic CORT exposure and developed a social stress paradigm, social instability stress (SIS), which exposes adult mice to unstable social hierarchies every 3 days for 7 weeks. Sex differences in response to chronic CORT emerged, with negative valence behaviors induced in CORT treated males, not females. SIS effectively induces negative valence behaviors in the open field, light dark, and novelty suppressed feeding tests, increases immobility in the forced swim test, and activates the hypothalamus-pituitary-adrenal (HPA) axis in both males and females. Importantly, while there were effects of estrous cycle on behavior, this variability did not impact the overall effects of SIS on behavior, suggesting estrous does not need to be tracked while utilizing SIS. Furthermore, the effects of SIS on negative valence behaviors were also reversed following chronic antidepressant treatment with fluoxetine (FLX) in both males and females. SIS also reduced adult hippocampal neurogenesis in female mice, while chronic FLX treatment increased adult hippocampal neurogenesis in both males and females. Overall, these data demonstrate that the SIS paradigm is an ethologically valid approach that effectively induces chronic stress in both adult male and adult female mice.