Corticosterone can act at the posterior paraventricular thalamus to inhibit hypothalamic-pituitary-adrenal activity in animals that habituate to repeated stress
Corticosterone can act at the posterior paraventricular thalamus to inhibit hypothalamic-pituitary-adrenal activity in animals that habituate to repeated stress
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DOI：
10.1210/en.2005-1393
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发表时间：
2006-10-01
期刊：
影响因子：
4.8
通讯作者：
Bhatnagar, Seema
中科院分区：
文献类型：
--
作者：
Jaferi, Azra;Bhatnagar, Seema
应激释放的糖皮质激素与糖皮质激素（GR）和/或盐皮质激素受体（MR）结合，对随后的下丘脑-垂体-肾上腺（HPA）应激反应产生负反馈。反馈抑制与HPA活性对重复暴露于相同（同型）应激源的习惯化有关。我们假设，后室旁丘脑（pPVTh）是一个网站，皮质酮的行为施加负反馈在反复的压力，这是很重要的习惯。如前所述，pPVTh抑制HPA反应的同型和异型的压力在反复，但不是急性，强调大鼠。我们进行了一系列的实验，涉及内pPVTh管理MR和/或GR激动剂或拮抗剂在不同的时间范围超过8天的约束。免疫细胞化学结果表明，pPVTh中存在MR和GR。急性内注射MR和/或GR拮抗剂的pPVTh前第八限制没有改变表达的习惯。因为习惯可能会发展之前的第8天，我们操纵GR和MR的pPVTh在整个8天的压力使用内pPVTh皮质酮植入物，这增强了习惯的第8天，而不影响急性应激反应。相反，每天内注射pPVTh GR和MR拮抗剂的第1 - 7天的限制防止习惯化的第8天。这些数据表明，皮质酮释放在重复的压力可以在GR和MR的pPVTh抑制HPA反应同型应激。我们还发现，在pPVTh项目的内侧前额叶皮层和基底外侧杏仁核，表明pPVTh诱导的HPA活性的抑制可能是介导的预测，这些选择边缘结构的一些GR细胞。
Glucocorticoids released by stress bind to glucocorticoid (GR) and/or mineralocorticoid receptors (MR) to exert negative feedback of subsequent hypothalamic-pituitary-adrenal (HPA) responses to stress. Feedback inhibition is implicated in habituation of HPA activity to repeated exposure to the same (homotypic) stressor. We hypothesized that the posterior paraventricular thalamus (pPVTh) is a site where corticosterone acts to exert negative feedback during repeated stress and that is important for habituation. As previously reported, the pPVTh inhibits HPA responses to homotypic and heterotypic stressors in repeatedly, but not acutely, stressed rats. We conducted a series of experiments involving intra-pPVTh administration of MR and/or GR agonists or antagonists during different time frames over 8 d of restraint. MR exist in the pPVTh, as do GR as shown by our immunocytochemical results. Acute intra-pPVTh injection of MR and/or GR antagonist before the eighth restraint did not alter expression of habituation. Because habituation may develop before d 8, we manipulated GR and MR in the pPVTh throughout 8 d of stress using intra-pPVTh corticosterone implants, which enhanced habituation on d 8 without affecting acute stress responses. Conversely, daily intra-pPVTh injections of GR and MR antagonists on d 1 - 7 of restraint prevented habituation on d 8. These data suggest that corticosterone released during repeated stress can act at GR and MR in the pPVTh to inhibit HPA responses to homotypic stress. We also found that some GR-containing cells in the pPVTh project to the medial prefrontal cortex and basolateral amygdala, suggesting that pPVTh-induced inhibition of HPA activity is potentially mediated by its projections to these select limbic structures.