Armario Antonio, Vallès Astrid, Dal-Zotto Silvina, Márquez Cristina, Belda Xavier
Departament de Biologia Cellular, de Fisiologia i d'Immunologia, Unitat de Fisiologia Animal, Facultat de Ciències Institut de Neurociències Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
Stress. 2004 Sep;7(3):157-72. doi: 10.1080/10253890400010721.
Although some laboratories have reported that a single session of stress is able to induce a long-lasting sensitisation of the hypothalamic-pituitary-adrenal (HPA) response to further exposures to stress, we have found that a single exposure to severe emotional (immobilisation, restraint or shock) or systemic (endotoxin) stressors reduces the responsiveness of the HPA to the same, but not to a novel (heterotypic), stressor, in which case a slight sensitisation was observed. Long-term desensitisation has been found to reduce not only secretion of peripheral HPA hormones (ACTH and corticosterone), but also to reduce responses of central components of the HPA axis (c-fos and CRF gene expression at the level of the paraventricular nucleus of the hypothalamus, PVN). In addition, desensitisation also applies to the impact of the stressor on food intake and, probably, to stress-induced hyperglycaemia. The development of long-term desensitisation of the HPA axis does not appear to be a universal consequence of exposure to severe stressors as it was not observed in response to insulin-induced hypoglycaemia. Whether or not the development of long-term effects of stress depend on the specific pathways activated by particular stressors remains to be tested. The observed desensitisation of the HPA axis in response to the homotypic stressor shows two special features which makes it difficult to be interpreted in terms of an habituation-like process: (a) the effect increased with time (days to weeks) elapsed between the first and second exposure to the stressor, suggesting a progressive maturational process; and (b) the stronger the stressor the greater the long-term desensitisation. Therefore, it is possible that desensitisation of the HPA axis is the sum of two different phenomena: long-term effects and habituation-like processes. The contribution of the former may be more relevant with severe stressors and longer inter-stress intervals, and that of the latter with mild stressors and repeated exposures. Long-term stress-induced changes may not take place at the level of the PVN itself, but in brain nuclei showing synaptic plasticity and putatively involved in the control of the HPA axis and other physiological responses. As for the precise areas involved, these remain to be characterized.
尽管一些实验室报告称，单次应激能够诱导下丘脑-垂体-肾上腺（HPA）轴对进一步应激暴露产生持久的敏感性，但我们发现，单次暴露于严重的情绪性（固定、束缚或电击）或全身性（内毒素）应激源会降低HPA轴对相同应激源的反应性，但对新的（异型）应激源则不会，在这种情况下会观察到轻微的敏感性增加。长期脱敏已被发现不仅会减少外周HPA激素（促肾上腺皮质激素和皮质酮）的分泌，还会降低HPA轴中枢成分的反应（下丘脑室旁核（PVN）水平的c-fos和促肾上腺皮质激素释放因子（CRF）基因表达）。此外，脱敏还适用于应激源对食物摄入的影响，可能也适用于应激诱导的高血糖症。HPA轴长期脱敏的发展似乎并非暴露于严重应激源的普遍后果，因为在胰岛素诱导的低血糖反应中未观察到这种情况。应激的长期影响的发展是否取决于特定应激源激活的特定途径仍有待测试。观察到的HPA轴对同型应激源的脱敏表现出两个特殊特征，这使得难以用类似习惯化的过程来解释：（a）效应随着第一次和第二次暴露于应激源之间经过的时间（数天至数周）而增加，表明这是一个渐进的成熟过程；（b）应激源越强，长期脱敏程度越大。因此，HPA轴的脱敏可能是两种不同现象的总和：长期效应和类似习惯化的过程。前者的贡献在严重应激源和较长的应激间隔时可能更相关，而后者在轻度应激源和重复暴露时更相关。长期应激诱导的变化可能不是发生在PVN本身的水平，而是发生在显示突触可塑性且可能参与HPA轴控制和其他生理反应的脑核中。至于具体涉及的区域，仍有待确定。
