Adversities during juvenility increase the risk for stress-related disorders, such as post-traumatic stress disorder (PTSD) and alcohol use disorder. However, stress can also induce coping mechanisms beneficial for later stressful experiences. We reported previously that mice selectively bred for high alcohol preference (HAP) exposed to stress during adolescence (but not during adulthood) showed enhanced fear-conditioned responses in adulthood, as measured by fear-potentiated startle (FPS). However, HAP mice also showed enhanced responding to safety cues predicting the absence of foot shocks in adulthood. Here, we pursue these findings in HAP mice by investigating in further detail how juvenile stress impacts the acquisition of safety and fear learning. HAP mice were subjected to three days of juvenile stress (postnatal days 25, 27, 28) and discriminative safety/fear conditioning in adulthood. FPS was used to assess safety versus fear cue discrimination, fear learning, and fear inhibition by the safety cue. Both stressed and unstressed HAP mice were able to discriminate between both cues as well as learn the fear cue-shock association. Interestingly, it was only the previously stressed mice that were able to inhibit their fear response when the fear cue was co-presented with the safety cue, thus demonstrating safety learning. We also report an incidental finding of alopecia in the juvenile stress groups, a phenotype seen in stress-related disorders. These results in HAP mice may be relevant to understanding the influence of juvenile trauma for individual risk and resilience toward developing PTSD and how individuals might benefit from safety cues in behavioral psychotherapy.

青少年时期的逆境会增加与压力相关的疾病的风险，例如创伤后应激障碍 (PTSD) 和酒精使用障碍。然而，压力也可以诱发对后来的压力经历有益的应对机制。我们之前报道过，在青春期（但不是在成年期）暴露于压力的高酒精偏好（HAP）选择性繁殖的小鼠在成年期表现出增强的恐惧条件反应，这可以通过恐惧强化惊吓（FPS）来衡量。然而，HAP 小鼠也表现出对预测成年期不存在足部电击的安全提示的增强反应。在这里，我们通过进一步详细调查幼年压力如何影响安全感和恐惧学习的获得，在 HAP 小鼠中追求这些发现。HAP 小鼠经受三天的幼年应激（出生后第 25、27、28）和成年期的歧视性安全/恐惧条件反射。FPS 用于评估安全性与恐惧提示歧视、恐惧学习和安全提示的恐惧抑制。压力和无压力的 HAP 小鼠都能够区分这两种线索，并学习恐惧线索与休克的关联。有趣的是，当恐惧提示与安全提示同时出现时，只有先前受到压力的小鼠能够抑制其恐惧反应，从而证明了安全学习。我们还报告了在青少年压力组中偶然发现的脱发，这是一种在压力相关疾病中可见的表型。HAP 小鼠的这些结果可能与了解青少年创伤对个体风险和对发展 PTSD 的复原力的影响以及个体如何从行为心理治疗中的安全提示中受益有关。