Chen X, Herbert J
Department of Anatomy, University of Cambridge, U.K.
Neuroscience. 1995 Feb;64(3):675-85. doi: 10.1016/0306-4522(94)00532-a.
Acute stress is known to evoke a discrete pattern of c-fos expression in the brain. The work reported here shows that this pattern is modified in regionally specific ways following repeated stress, and that this can be correlated with changes in telemetered heart rate, core temperature and corticosterone output that occur during adaptation. Intact male rats were restrained for 60 min daily for one or 10 days. Stress-induced tachycardia was maximal 10 min following the onset of restraint, and decreased thereafter. The peak value was not altered by repeated restraint, but levels fell towards baseline values more rapidly with increasing bouts of stress. Core temperature showed marked reduction during the first 10 min of the initial stress, followed by a minor (and not very consistent) overshoot during the remainder of the stress period. In contrast to heart rate, stress-induced hypothermia did not alter during repeated restraint. Corticosterone was raised dramatically immediately following the first 60-min session of restraint, and this was attenuated by repeated stress. Sixty minutes after the end of the first stress session, there was pronounced c-fos expression in the lateral septum, lateral preoptic area, lateral hypothalamic area, all divisions of the hypothalamic paraventricular nucleus, the medial (but not central) amygdala, the locus ceruleus and a brainstem structure (thought to be Barrington's nucleus), compared to rats transferred to the testing room but not restrained. Sixty minutes after the 10th stress session, c-fos expression was markedly decreased in some of these areas compared with the pattern observed after the first stress, especially in the paraventricular nucleus (dorsal and medial parvicellular regions) and in medial amygdala. However, all other areas measured demonstrated a sustained response even after repeated stress. There were no significant differences in c-fos expression in rats repeatedly transferred to the testing room (but not stressed) compared to singly transferred counterparts. These results show that both neuronal and physiological responses adapt to a repeated stress, but that in both cases this has highly specific components. It seems likely that adaptive changes in c-fos expression are associated with those in some features of autonomic and endocrine reactions. It is noteworthy that there is evidence that the lateral septum, in which c-fos expression did not diminish after repeated stress, may be involved in temperature control, whereas the paraventricular nucleus, in which c-fos did alter, has been linked with both cardiac and corticoid regulation.
已知急性应激会在大脑中引发离散的c-fos表达模式。此处报告的研究表明，在反复应激后，这种模式会以区域特异性方式发生改变，并且这可能与适应过程中遥测心率、核心体温和皮质酮分泌的变化相关。将完整的雄性大鼠每天束缚60分钟，持续1天或10天。应激诱导的心动过速在束缚开始后10分钟时达到最大值，此后下降。重复束缚并未改变峰值，但随着应激次数的增加，心率水平更快地降至基线值。在初次应激的前10分钟内，核心体温显著降低，随后在应激期的剩余时间内出现轻微（且不太一致）的体温过高。与心率不同，应激诱导的体温过低在重复束缚期间没有改变。在首次60分钟的束缚结束后，皮质酮立即显著升高，而重复应激会使其减弱。在首次应激结束60分钟后，与转移到测试室但未受束缚的大鼠相比，外侧隔区、外侧视前区、外侧下丘脑区、下丘脑室旁核的所有亚区、内侧（而非中央）杏仁核、蓝斑和一个脑干结构（被认为是巴林顿核）中有明显的c-fos表达。在第10次应激结束60分钟后，与首次应激后观察到的模式相比，这些区域中的一些区域c-fos表达明显降低，尤其是在室旁核（背侧和内侧小细胞区）和内侧杏仁核。然而，即使在反复应激后，所有其他测量区域仍表现出持续的反应。与单次转移的大鼠相比，反复转移到测试室（但未应激）的大鼠在c-fos表达上没有显著差异。这些结果表明，神经元和生理反应都会适应反复应激，但在这两种情况下，这种适应都具有高度特异性的成分。c-fos表达的适应性变化似乎与自主神经和内分泌反应的某些特征变化有关。值得注意的是，有证据表明，反复应激后c-fos表达未减少的外侧隔区可能参与体温调节，而c-fos确实发生改变的室旁核则与心脏和皮质类固醇调节有关。
