Sensitization of restraint-induced corticosterone secretion after chronic restraint in rats: involvement of 5-HT₇ receptors.
Sensitization of restraint-induced corticosterone secretion after chronic restraint in rats: involvement of 5-HT₇ receptors.
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DOI：
10.1016/j.neuropharm.2013.03.013
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发表时间：
2013-08
影响因子：
4.7
通讯作者：
Terrón JA
中科院分区：
文献类型：
--
作者：
García-Iglesias BB;Mendoza-Garrido ME;Gutiérrez-Ospina G;Rangel-Barajas C;Noyola-Díaz M;Terrón JA
5-羟色胺（5-HT）调节下丘脑-垂体-肾上腺（HPA）轴对应激的反应。我们研究了慢性束缚应激的影响（CRS; 20分钟/天）与对照（CTRL）条件下持续14天相比，1）在用溶剂或SB-656104预处理的大鼠中束缚诱导的ACTH和皮质酮（CORT）分泌（5-HT 7受体拮抗剂）; 2）5-HT 7受体样免疫反应性下丘脑室旁核（PVN）和肾上腺（AG）内5-HT 7-LI和蛋白表达; 3）PVN和AG中5-HT和5-羟基吲哚乙酸（5-HIAA）的基线水平以及5-HIAA/5-HT比率;以及4）AG中的5-HT样免疫反应性（5-HT-LI）以及PVN和AG中的色氨酸羟化酶（TPH）蛋白。在第15天，将动物再分为处理组和无处理组。给药组动物接受溶媒或SB-656104腹腔注射;未给药组动物未接受注射。60分钟后，将处理动物断头，无进一步应激（0分钟）或进行急性束缚（10、30、60或120分钟）;测量激素血清水平。其余测量未使用治疗动物。CRS降低体重增加并增加肾上腺重量。在CTRL动物中，急性束缚以时间依赖性方式增加ACTH和CORT分泌; SB-656104抑制了这两种反应。与对照条件相比，暴露于CRS消除了ACTH，但放大了CORT对束缚的反应; SB-656104对ACTH水平无影响，但显著抑制了致敏CORT反应。在对照组动物，5-HT 7-LI在室旁核的大细胞和小细胞亚群中检测到，在肾上腺皮质中稀疏。CRS暴露使PVN中5-HT 7-LI和蛋白质含量降低，但使肾上腺皮质中5-HT 7-LI和整个AG中蛋白质含量升高。CRS动物的PVN和AG中检测到较高的5-HT和5-HIAA水平，但仅AG中的5-HIAA/5-HT比值升高。最后，尽管在CTRL动物的肾上腺皮质中稀疏地观察到5-HT-LI，但在CRS动物的肾上腺皮质中强烈增加。在两组动物的AG中均未检测到TPH蛋白。结果表明，CRS促进内分泌干扰涉及减少ACTH和敏化CORT反应急性约束。这种现象可能与AG中5-HT 7受体的功能和表达增加以及5-HT周转有关。
Serotonin (5-HT) modulates the hypothalamic-pituitary-adrenal (HPA) axis response to stress. We examined the effect of chronic restraint stress (CRS; 20 min/day) as compared to control (CTRL) conditions for 14 days, on: 1) restraint-induced ACTH and corticosterone (CORT) secretion in rats pretreated with vehicle or SB-656104 (a 5-HT7 receptor antagonist); 2) 5-HT7 receptor-like immunoreactivity (5-HT7-LI) and protein in the hypothalamic paraventricular nucleus (PVN) and adrenal glands (AG); 3) baseline levels of 5-HT and 5-hydroxyindolacetic acid (5-HIAA), and 5-HIAA/5-HT ratio in PVN and AG; and 4) 5-HT-like immunoreactivity (5-HT-LI) in AG and tryptophan hydroxylase (TPH) protein in PVN and AG. On day 15, animals were subdivided into Treatment and No treatment groups. Treatment animals received an i.p. injection of vehicle or SB-656104; No Treatment animals received no injection. Sixty min later, Treatment animals were either decapitated with no further stress (0 min) or submitted to acute restraint (10, 30, 60 or 120 min); hormone serum levels were measured. No Treatment animals were employed for the rest of measurements. CRS decreased body weight gain and increased adrenal weight. In CTRL animals, acute restraint increased ACTH and CORT secretion in a time of restraint-dependent manner; both responses were inhibited by SB-656104. Exposure to CRS abolished ACTH but magnified CORT responses to restraint as compared to CTRL conditions; SB-656104 had no effect on ACTH levels but significantly inhibited sensitized CORT responses. In CTRL animals, 5-HT7-LI was detected in magnocellular and parvocellular subdivisions of PVN and sparsely in adrenal cortex. Exposure to CRS decreased 5-HT7-LI and protein in the PVN, but increased 5-HT7-LI in the adrenal cortex and protein in whole AG. Higher 5-HT and 5-HIAA levels were detected in PVN and AG from CRS animals but 5-HIAA/5-HT ratio increased in AG only. Finally, whereas 5-HT-LI was sparsely observed in the adrenal cortex of CTRL animals, it strongly increased in the adrenal cortex of CRS animals. No TPH protein was detected in AG from both animal groups. Results suggest that CRS promotes endocrine disruption involving decreased ACTH and sensitized CORT responses to acute restraint. This phenomenon may be associated with increased function and expression of 5-HT7 receptors as well as 5-HT turnover in AG.
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