Acute physical or psychological stress can elicit adaptive behaviors that allow an organism maintain homeostasis. However, intense and/or prolonged stressors often have the opposite effect, resulting in maladaptive behaviors and curbing goal-directed action; in the extreme, this may contribute to the development of psychiatric conditions like generalized anxiety disorder, major depressive disorder, or post-traumatic stress disorder. While treatment of these disorders generally focuses on reducing reactivity to potentially threatening stimuli, there are in fact impairments across multiple domains including valence, arousal, and cognition. Here, we use the genetically stress-susceptible 129S1 mouse strain to explore the effects of stress across multiple domains. We find that 129S1 mice exhibit a potentiated neuroendocrine response across many environments and paradigms, and that this is associated with reduced exploration, neophobia, decreased novelty- and reward-seeking, and spatial learning and memory impairments. Taken together, our results suggest that the 129S1 strain may provide a useful model for elucidating mechanisms underlying myriad aspects of stress-linked psychiatric disorders as well as potential treatments that may ameliorate symptoms.

急性生理或心理压力会引发适应性行为，使有机体保持体内平衡。然而，强烈和/或长期的压力源往往会产生相反的效果，导致适应不良的行为并抑制目标导向的行动；在极端情况下，这可能会导致精神疾病的发展，如广泛性焦虑症、重度抑郁症或创伤后应激障碍。虽然这些疾病的治疗通常侧重于减少对潜在威胁刺激的反应，但实际上存在多个领域的损伤，包括效价、唤醒和认知。在这里，我们使用对遗传压力敏感的 129S1 小鼠品系来探索压力对多个领域的影响。我们发现 129S1 小鼠在许多环境和范式中表现出增强的神经内分泌反应，这与探索减少、新恐惧症、新奇和寻求奖励减少以及空间学习和记忆障碍有关。总之，我们的研究结果表明，129S1 菌株可能提供一个有用的模型，用于阐明与压力相关的精神疾病的无数方面的潜在机制以及可能改善症状的潜在治疗方法。