Involvement of neuropeptides in the hypothalamus and limbic system in the adaptation of stress response

为了阐明下丘脑垂体肾上腺轴（HPA）和神经内分泌免疫系统对应激的适应过程，采用Wister雄性大鼠进行了三项实验。结果如下：持续16小时的长时间约束应激可引起适应性变化，其特征是下丘脑室旁核（PVN）和血浆促肾上腺皮质激素（ACTH） c-fos mRNA/Fos蛋白表达瞬间升高并逐渐恢复到基础水平，在许多总白细胞和一些淋巴细胞亚群中，尽管循环皮质酮（CORT）保持在高水平，但c-fos mRNA/Fos蛋白表达在缓慢恢复后短暂下降。在16小时约束大鼠中观察到冷应激诱导PVN旁细胞区c-fos mRNA/Fos的叠加再表达。c-fos基因在叠加冷应激大鼠中的表达程度与单冷应激大鼠（正常反应）的表达程度相同。与单一冷应激大鼠相比，叠加冷应激大鼠的血浆AC、TH水平显著升高（超反应、易化）。2 .合并冷应激大鼠血浆CORT水平与单一冷应激大鼠血浆CORT水平无显著差异（无超反应）。重复约束应激（1小时/天）大鼠在7 d和14 d时，与第1天相比，PVN血浆ACTH和CORT水平、c-fos mRNA和AVP异核RNA表达均呈下降趋势（习惯化）。另一方面，重复低温（4℃）+约束应激大鼠未观察到这些反应的习惯化。这些结果表明，应激反应的适应可能发生在各种应激情境中，对叠加应激源的应激反应可能在HPA轴的各个水平上以不同的方式发生，对重复应激源的应激反应的习惯化或促进可能与应激源的种类有关。少

In order to clarify the processes of adaptation to stress in hypothalamic pituitary adrenal (HPA) axis and neuroendocrinoimmune system, three experiments were performed using Wister male rats.The results were following.1. A long-duration restraint stress for 16 hours evoked adaptive change, characterized by transient increase and gradual recovery to basal level in c-fos mRNA/Fos protein expression in the hypothalamic paraventricular nucleus (PVN) and in plasma adrenocorticotropin (ACTH) levels, and transient decrease following slow recovery in a number of total white blood cells and some lymphocytes subpopulations, although circulating corticosterone (CORT) remained at high level.2. Superimposed cold stress-induced re-expression of c-fos mRNA/Fos in the parvocellular region of the PVN was observed in 16 hours restraint rats. The degree of expression of c-fos gene in superimposed cold stress rats was the same as those observed in single cold stress rats (normo-responsive). The plasma AC … More TH levels in superimposed cold stress rats were significantly higher compared with those in single cold stress rats (hyper-responsive, facilitation). There was no significant differences between plasma CORT level s superimposed cold stress rats and those in single cold stress rats (not hyper-responsive).3. The plasma ACTH and CORT levels, c-fos mRNA and AVP heteronuclear RNA expression in the PVN in the repeated restraint stress (1 hour/day) rats showed the decreasing tendency (habituation) at 7 days and 14 days later comparing with those at the first experiment day. On the other hand, the habituation of these responses was not observed in repeated cold (4℃)+restraint stress rats.These results suggest that adaptation of stress response may occur in various stressful situation and the stress response to a superimposed stressor may occur in a different way at each level of the HPA axis, and that occurrence of habituation or facilitation of stress response to repeated stressors may related the sort of stressors. Less