Lopez-Kawa Sofia A, Lattal K Matthew
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon 97239, USA.
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon 97239, USA
Learn Mem. 2025 Aug 7;32(7-8). doi: 10.1101/lm.054097.125. Print 2025 Jul-Aug.
Individuals diagnosed with post-traumatic stress disorder (PTSD) are hyperresponsive to otherwise ordinary stimuli (e.g., loud noises or certain smells) long after a traumatic experience. At a preclinical level, this persistent effect of trauma is captured in stress-enhanced fear learning (SEFL), in which a stressful experience in one context causes a persistent increase in fear conditioning with a mild stressor in a second context. Here, we characterized multiple behaviors (including freezing, rearing, darting, and jumping) in male and female Long-Evans rats during SEFL. Rats received a battery of foot shocks in one context followed by a mild stressor (single foot shock) in a second context. We found that males and females with a history of multiple shocks in one context had higher freezing levels during the SEFL test, relative to no shock controls, and that this SEFL effect persisted to a second test 30 days later. The dominant response was freezing in males and females, with no reliable sex differences at any stage of the SEFL procedure, but females also showed some unique escape-like behaviors on the days of trauma and mild stress exposure. In addition, females in the proestrus and estrus phases of the estrous cycle during the initial shock exposure showed increased SEFL relative to females in the metestrus and diestrus phases. These findings suggest that males and females show similar SEFL effects with freezing behavior, but that ovarian cycle phase at the time of trauma may alter the strength of SEFL in females.
被诊断患有创伤后应激障碍（PTSD）的个体，在创伤经历很久之后，会对原本普通的刺激（如巨大噪音或某些气味）产生过度反应。在临床前水平上，创伤的这种持续影响在应激增强恐惧学习（SEFL）中有所体现，即在一种情境下的应激经历会导致在第二种情境中对轻度应激源的恐惧条件反射持续增加。在此，我们对雄性和雌性Long-Evans大鼠在SEFL过程中的多种行为（包括僵住、站立、飞奔和跳跃）进行了特征描述。大鼠在一种情境下接受一系列足部电击，随后在第二种情境中接受轻度应激源（单次足部电击）。我们发现，相对于无电击对照组，在一种情境下有多次电击经历的雄性和雌性大鼠在SEFL测试期间僵住水平更高，且这种SEFL效应在30天后的第二次测试中仍然存在。雄性和雌性的主要反应都是僵住，在SEFL过程的任何阶段都没有可靠的性别差异，但雌性在创伤和轻度应激暴露当天也表现出一些独特的类似逃避的行为。此外，在初次电击暴露期间处于发情周期动情前期和发情期的雌性，相对于处于动情后期和动情间期的雌性，表现出更强的SEFL。这些发现表明，雄性和雌性在僵住行为方面表现出相似的SEFL效应，但创伤时的卵巢周期阶段可能会改变雌性的SEFL强度。
