Social stress exposure heightens the risk of substance abuse disorder development, especially when endured during adolescence, influencing long-term mental health. This study investigates early-life stress's potential to confer resilience against later-life stressors. To investigate this hypothesis, we examined the impact of a single social defeat (SD) incident during adolescent mice's lives on subsequent voluntary ethanol consumption following repeated adult social stress exposure. Half of the adolescent mice experienced SD at postnatal day 28. Three weeks later (postnatal day 49), defeated groups encountered four confrontations with aggressive residents every 72 hours, while control groups were exposed to non-resident exploration. A day after the last SD, defeated mice were classified as resilient or susceptible based on their response to a social interaction test (SIT), a model for depressive behavior. To assess ethanol consumption during young adulthood, researchers used the ‘drinking in the dark’ and oral ethanol self-administration paradigms. Stress inoculation (IS) slightly increased resilient animals in the SIT. In mice without IS exposure during adolescence, susceptible defeated mice displayed higher ethanol consumption and motivation than control and resilient mice. IS in adolescence effectively counteracted this effect, as IS-SD groups, whether resilient or susceptible, showed no increase in ethanol intake. These groups also exhibited similar motivation to control, measured by the progressive ratio. Notably, elevated IL-6 levels seen in SD-S mice were absent in IS-exposed mice. Additionally, IS-exposed groups had lower prefrontal cortex IL-6 and CX3CL1 levels. These findings support the hypothesis that IS, induced by moderate-intensity stress during adolescence, can enhance resilience to more severe stressors in adulthood.

暴露于社会压力会增加药物滥用障碍的风险，尤其是在青春期时，会影响长期的心理健康。这项研究调查了早期生活压力是否有可能赋予人们抵御晚年压力的能力。为了研究这一假设，我们研究了青春期小鼠生活中的一次社交失败（SD）事件对成年小鼠反复暴露于社交压力后随后自愿乙醇消耗的影响。一半的青春期小鼠在出生后第 28 天经历了 SD。三周后（出生后第 49 天），失败组每 72 小时就会遇到四次与攻击性居民的对抗，而对照组则接受非居民探索。最后一次 SD 一天后，失败的小鼠根据其对社交互动测试（SIT）（抑郁行为模型）的反应被分类为有弹性或易受影响。为了评估青年时期的乙醇消耗量，研究人员使用了“黑暗中饮酒”和口服乙醇自我给药范例。应激接种（IS）略微提高了 SIT 动物的恢复能力。在青春期未暴露于 IS 的小鼠中，易感失败小鼠比对照小鼠和复原小鼠表现出更高的乙醇消耗和动机。青春期的 IS 有效地抵消了这种影响，因为 IS-SD 群体，无论是有弹性的还是易受影响的，都没有表现出乙醇摄入量的增加。这些群体也表现出类似的控制动机，通过进步比率来衡量。值得注意的是，在 SD-S 小鼠中观察到的 IL-6 水平升高在 IS 暴露的小鼠中不存在。此外，IS 暴露组的前额皮质 IL-6 和 CX3CL1 水平较低。这些发现支持这样的假设：青春期中等强度压力诱发的 IS 可以增强成年期对更严重压力源的恢复能力。