Hypothalamic-pituitary-adrenal response to chronic stress in five inbred rat strains: Differential responses are mainly located at the adrenocortical level
Hypothalamic-pituitary-adrenal response to chronic stress in five inbred rat strains: Differential responses are mainly located at the adrenocortical level
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DOI：
10.1159/000126973
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发表时间：
1996-04-01
影响因子：
4.1
通讯作者：
Armario, A
中科院分区：
文献类型：
--
作者：
Gomez, F;Lahmame, A;Armario, A
本实验观察了慢性应激对Brown Norway（BN）、Fischer（FIS）、刘易斯（LEW）、Spontaneous Hypertensive（SHR）和Wistar京都（WKY）五个品系大鼠下丘脑-垂体-肾上腺皮质（HPA）轴的影响。以前，这些大鼠品系在强迫游泳试验中显示出明显的行为差异，该试验可能测量抑郁样行为，BN和WKY比其他品系更被动。在这里，我们测试的假设，行为不动的差异可能与异常HPA反应慢性固定（IMO）的压力。在基础条件下（早晨），不同品系大鼠肾上腺重量、血清促肾上腺皮质激素（ACTH）和皮质酮（B）水平、下丘脑室旁核（PVN）和海马糖皮质激素和盐皮质激素受体（GR和MR）mRNA水平无明显差异。慢性IMO后，LEW、SHR和WKY大鼠的基础血清ACTH水平升高，但BN或FIS大鼠不升高，而BN、FIS、SHR和WKY大鼠的基础B水平升高，但LEW大鼠不升高。肾上腺重量的增加也是应变依赖性的，与慢性IMO诱导的高皮质酮血症呈负相关。在中央水平上没有观察到菌株之间的这些外周差异。因此，慢性IMO增加CRF mRNA含量的PVN，原位杂交分析，类似于在所有菌株。此外，慢性IMO后，海马GR mRNA和RM mRNA的含量在品系间无差异。综合所有品系的数据，慢性IMO降低了海马CA 1、CA 3和DG区的GR mRNA含量（50-60%），并轻微降低了CA 1和CA 3区的MR mRNA水平（11-13%）。结果表明：（1）慢性IMO使海马GR mRNA表达下调，下丘脑室旁核CRF mRNA表达上调;（2）慢性IMO后血清ACTH和B水平及肾上腺皮质肥大在各品系间存在差异;（iii）血清B水平和肾上腺重量的变化与ACTH的变化无关，因此某些变化可能位于肾上腺水平;（iv）在LEW和WKY大鼠中，B对慢性IMO的低反应性可能与肾上腺对ACTH的低敏感性有关，（v）慢性IMO程序诱导的HPA轴变化与先前报道的BN和WKY在强迫游泳试验中的抑郁样行为数据无关。
The effects of chronic stress on the hypothalamic-pituitary-adrenocortical (HPA) axis were studied in five inbred rat strains, i.e. Brown Norway (BN), Fischer (FIS), Lewis (LEW), Spontaneously Hypertensive (SHR) and Wistar Kyoto (WKY). Previously, these rat strains had been shown to display clear behavioral differences in the forced swimming test that presumably measures depression-like behavior, BN and WKY being more passive than the other strains. Here we test the hypothesis that the differences in behavioral immobility might be associated with an abnormal HPA response to chronic immobilization (IMO) stress. In stress-naive rats under basal conditions (morning) there were no differences among strains in adrenal weight, serum adrenocorticotropin hormone (ACTH) and corticosterone (B) levels, corticotropin-releasing factor (CRF) mRNA in the hypothalamic paraventricular nucleus (PVN) and hippocampal glucocorticoid and mineralocorticoid receptor (GR and MR) mRNA. After chronic IMO, basal serum ACTH levels were increased in LEW, SHR and WKY, but not in BN or FIS rats, whereas basal B levels were increased in BN, FIS, SHR and WKY rats, but not in LEW. The increase in adrenal weight was also strain dependent and correlated negatively with chronic IMO-induced hypercorticosteronemia. These peripheral differences among strains were not observed at central levels. Thus, chronic IMO increased the CRF mRNA content in the PVN, analyzed by in situ hybridization, similarly in all strains. In addition, after chronic IMO no differences were found among strains in hippocampal GR mRNA and RM mRNA contents. Considering data from all strains together, chronic IMO reduced the GR mRNA (50-60%) content in the hippocampal CA1, CA3 and DG areas, and slightly diminished (11-13%) MR mRNA levels in CA1 and CA3 areas. The present results indicate that: (i) chronic IMO down-regulates GR mRNA in the hippocampus and slightly up-regulates CRF mRNA in the hypothalamic PVN similarly in all strains; (ii) after chronic IMO interstrain differences were observed in serum ACTH and B levels as well as adrenal hypertrophy; (iii) some changes are probably located at the adrenal level since changes in serum B level and adrenal weight were not related to changes in ACTH; (iv) in LEW and WKY rats, B hyporesponsiveness to chronic IMO might be linked to low adrenal sensitivity to ACTH, and (v) HPA axis changes induced by the chronic IMO procedure are not related to previously reported data on depressive-like behavior of BN and WKY in the forced swimming test.