Institut de Neurociències, Universitat Autònoma de Barcelona, Spain; Animal Physiology Unit, School of Biosciences, Universitat Autònoma de Barcelona, Spain.
Institut de Neurociències, Universitat Autònoma de Barcelona, Spain; Psychobiology Unit, School of Psychology, Universitat Autònoma de Barcelona, Spain.
Horm Behav. 2018 Jul;103:7-18. doi: 10.1016/j.yhbeh.2018.05.017. Epub 2018 May 30.
Exposure to electric foot-shocks can induce in rodents contextual fear conditioning, generalization of fear to other contexts and sensitization of the hypothalamic-pituitary-adrenal (HPA) axis to further stressors. All these aspects are relevant for the study of post-traumatic stress disorder. In the present work we evaluated in rats the sex differences and the role of early life stress (ELS) in fear memories, generalization and sensitization. During the first postnatal days subjects were exposed to restriction of nesting material along with exposure to a "substitute" mother. In the adulthood they were exposed to (i) a contextual fear conditioning to evaluate long-term memory and extinction and (ii) to a novel environment to study cognitive fear generalization and HPA axis heterotypic sensitization. ELS did not alter acquisition, expression or extinction of context fear conditioned behavior (freezing) in either sex, but reduced activity in novel environments only in males. Fear conditioning associated hypoactivity in novel environments (cognitive generalization) was greater in males than females but was not specifically affected by ELS. Although overall females showed greater basal and stress-induced levels of ACTH and corticosterone, an interaction between ELS, shock exposure and sex was found regarding HPA hormones. In males, ELS did not affect ACTH response in any situation, whereas in females, ELS reduced both shock-induced sensitization of ACTH and its conditioned response to the shock context. Also, shock-induced sensitization of corticosterone was only observed in males and ELS specifically reduced corticosterone response to stressors in males but not females. In conclusion, ELS seems to have only a minor impact on shock-induced behavioral conditioning, while affecting the unconditioned and conditioned responses of HPA hormones in a sex-dependent manner.
电击暴露可诱导啮齿动物产生情境性恐惧条件反射，将恐惧泛化到其他情境，并使下丘脑-垂体-肾上腺（HPA）轴对进一步的应激源敏感。所有这些方面都与创伤后应激障碍的研究相关。在本工作中，我们评估了大鼠中的性别差异以及早期生活应激（ELS）在恐惧记忆、泛化和敏感化中的作用。在出生后的头几天，实验对象被限制接触筑巢材料，并暴露于“替代”母亲。在成年期，它们被暴露于（i）情境性恐惧条件反射，以评估长期记忆和消退，以及（ii）新颖环境，以研究认知性恐惧泛化和 HPA 轴异型敏感化。ELS 并未改变雄性或雌性的情境性恐惧条件反射行为（冻结）的获得、表达或消退，但仅降低雄性的新环境中的活动。与恐惧条件反射相关的新环境中的低活性（认知泛化）在雄性中比在雌性中更大，但不受 ELS 的具体影响。尽管女性总体上表现出更高的基础和应激诱导的促肾上腺皮质激素（ACTH）和皮质酮水平，但 HPA 激素的性别之间存在 ELS、电击暴露和性别的相互作用。在雄性中，ELS 不影响任何情况下的 ACTH 反应，而在雌性中，ELS 降低了 ACTH 对电击的诱导性敏感化及其对电击情境的条件反应。此外，仅在雄性中观察到应激诱导的皮质酮敏感化，而 ELS 特异性地降低了雄性而非雌性的应激源对皮质酮的反应。总之，ELS 似乎对电击诱导的行为条件反射只有较小的影响，而以性别依赖的方式影响 HPA 激素的非条件和条件反应。
