Belda Xavier, Rotllant David, Fuentes Silvia, Delgado Raúl, Nadal Roser, Armario Antonio
Institute of Neurosciences, Autonomous University of Barcelona, Barcelona, Spain.
Ann N Y Acad Sci. 2008 Dec;1148:165-73. doi: 10.1196/annals.1410.038.
Exposure to some predominantly emotional (electric shock) and systemic (interleukin-1beta) stressors has been found to induce long-term sensitization of the hypothalamic-pituitary-adrenal (HPA) responsiveness to further superimposed stressors. Since exposure to immobilization on wooden boards (IMO) is a severe stressor and may have interest regarding putative animal models of post-traumatic stress disorders (PTSD), we have characterized long-lasting effects of a single exposure to IMO and other stressors on the HPA response to the same (homotypic) and to novel (heterotypic) stressors and the putative mechanisms involved. A single exposure to IMO caused a long-lasting reduction of peripheral and central responses of the HPA axis, likely to be mediated by some brain areas, such as the lateral septum and the medial amygdala. This desensitization is not explained by changes in negative glucocorticoid feedback, and, surprisingly, it is positively related to the intensity of the stressors. In contrast, the HPA response to heterotypic stressors (novel environments) was enhanced, with maximal sensitization on the day after IMO. Sensitization progressively vanished over the course of 1-2 weeks and was not modulated by IMO-induced corticosterone release. Moreover, it could not be explained by changes in the sensitivity of the HPA axis to fast or intermediate/delayed negative feedback, as evaluated 1 week after exposure to IMO, using shock as the heterotypic stressor. Long-lasting stress-induced behavioral changes reminiscent of enhanced anxiety and HPA sensitization are likely to be parallel but partially independent phenomena, the former being apparently not related to the intensity of stressors.
研究发现，暴露于一些主要为情绪性（电击）和全身性（白细胞介素-1β）应激源会诱导下丘脑-垂体-肾上腺（HPA）轴对进一步叠加应激源的长期敏感化。由于暴露于木板束缚（IMO）是一种严重的应激源，可能对创伤后应激障碍（PTSD）的假定动物模型具有研究意义，我们已经描述了单次暴露于IMO和其他应激源对HPA轴对相同（同型）和新的（异型）应激源的反应以及相关假定机制的长期影响。单次暴露于IMO导致HPA轴的外周和中枢反应长期降低，这可能由一些脑区介导，如外侧隔区和杏仁核内侧。这种脱敏现象不能用负性糖皮质激素反馈的变化来解释，令人惊讶的是，它与应激源的强度呈正相关。相反，HPA轴对异型应激源（新环境）的反应增强，在IMO后的第二天达到最大敏感化。敏感化在1-2周内逐渐消失，并且不受IMO诱导的皮质酮释放的调节。此外，正如在暴露于IMO 1周后使用电击作为异型应激源所评估的那样，它不能用HPA轴对快速或中间/延迟负反馈的敏感性变化来解释。长期应激诱导的行为变化让人联想到焦虑增强和HPA敏感化，它们可能是平行但部分独立的现象，前者显然与应激源的强度无关。
