Institut de Neurociències, Spain; Animal Physiology Unit (Department of Cellular Biology, Physiology and Immunology), Faculty of Biosciences, Universitat Autònoma de Barcelona, Spain.
Institut de Neurociències, Spain; Psychobiology Unit, Faculty of Psychology, Universitat Autònoma de Barcelona, Spain.
Horm Behav. 2020 Nov;126:104865. doi: 10.1016/j.yhbeh.2020.104865. Epub 2020 Oct 6.
Traumatic events have been proposed to be associated with hypo-activity of the hypothalamic-pituitary-adrenal (HPA) axis, but data in animal models exposed to severe stressors are controversial and have important methodological concerns. Individual differences in resting or stress levels of corticosterone might explain some of the inconsistencies. We then studied this issue in male rats exposed to 2 h immobilization on boards (IMO), a severe stressor. Thirty-six rats were blood sampled under resting conditions four times a day on three non-consecutive days. Then, they were assigned to control (n = 14) or IMO (n = 22) to study the HPA response to IMO, the stressor-induced alterations in the circadian pattern of corticosterone (CPCORT), and the behavioral and HPA responsiveness to an open-field. Individual differences in pre-IMO resting corticosterone were inconsistent, but averaging data markedly improved consistency. The CPCORT was markedly altered on day 1 post-IMO (higher trough and lower peak levels), less altered on day 3 and apparently normal on day 7. Importantly, when rats were classified in low and high resting corticosterone groups (LCORT and HCORT, respectively), on the basis of the area under the curve (AUC) of the averaged pre-IMO data, AUC differences between LCORT and HCORT groups were maintained in controls but disappeared in IMO rats during the post-IMO week. Open-field hypo-activity and corticosterone sensitization were similar in LCORT and HCORT groups nine days after IMO. A single IMO exposure causes long-lasting HPA alterations, some of them dependent on pre-stress resting corticosterone levels, with no evidence for post-IMO resting corticosterone hypo-activity.
创伤性事件被认为与下丘脑-垂体-肾上腺（HPA）轴的低活性有关，但暴露于严重应激源的动物模型中的数据存在争议，并且存在重要的方法学问题。皮质酮的静息或应激水平的个体差异可能解释了其中的一些不一致性。然后，我们在暴露于 2 小时板上固定（IMO）的雄性大鼠中研究了这个问题，IMO 是一种严重的应激源。36 只大鼠在三天内不连续的四天内每天四次在静息条件下采血。然后，他们被分配到对照组（n = 14）或 IMO 组（n = 22），以研究 IMO 对 HPA 的反应、应激诱导的皮质酮昼夜节律变化（CPCORT）以及开放场的行为和 HPA 反应性。IMO 前静息皮质酮的个体差异不一致，但平均数据明显提高了一致性。IMO 后第 1 天 CPCORT 明显改变（低谷和高峰水平升高），第 3 天改变较小，第 7 天明显正常。重要的是，当根据平均 IMO 前数据的曲线下面积（AUC）将大鼠分为低和高静息皮质酮组（LCORT 和 HCORT）时，LCORT 和 HCORT 组之间的 AUC 差异在对照组中得以维持，但在 IMO 大鼠中消失在 IMO 后一周。IMO 后 9 天，开放场活动减少和皮质酮敏化在 LCORT 和 HCORT 组中相似。单次 IMO 暴露会导致长期的 HPA 改变，其中一些改变依赖于应激前静息皮质酮水平，而 IMO 后没有证据表明静息皮质酮活性降低。
