Anti-stress effects of combined glucocorticoid and mineralocorticoid receptor blockade in the paraventricular nucleus of the hypothalamus.

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Mineralocorticoid receptors (MRs), glucocorticoid receptors (GRs) and corticotropin-releasing factor (CRF) in the paraventricular nucleus of hypothalamus (PVN) are implicated in stress response. The present study investigated the role of GRs and MRs in the PVN in regulating depressive and anxiety-like behaviors.To model chronic stress, rats were exposed to corticosterone treatment via drinking water for 21 days, and GR antagonist RU486 and MR antagonist spironolactone, alone and combined, were directly injected in the PVN daily for the last 7 days corticosterone treatment. Behavioral tests were run on days 22 and 23. Depressive- and anxiety-like behaviors were evaluated in forced swim test, sucrose preference test, novelty-suppressed feeding test and social interaction test. The expression of GRs, MRs and CRF were detected by Western-Blot.The rats exposed to corticosterone exhibited depressive- and anxiety-like behaviors. The expression of GRs and MRs decreased, and CRF levels increased in the PVN. The intra-PVN administration of RU486 increased the levels of GRs and CRF without influencing depressive- or anxiety-like behaviors. The spironolactone-treated group exhibited an increase in MRs without influencing GRs and CRF in the PVN, and improved anxiety-like behaviors. Interestingly, the intra-PVN administration of RU486 and spironolactone combined restored the expression of GRs, MRs, and CRF and improved depressive- and anxiety-like behaviors.These results suggest that the simultaneous restoration of GRs, MRs, and CRF in the PVN in this rat model of stress might play an important role in the treatment of depression and anxiety.

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Authors: Hui Ding, Su-Ying Cui, Xiang-Yu Cui, Yu-Tong Liu, Xiao Hu, Hui-Ling Zhao, Yu Qin, Nurhumar Kurban, Yong-He Zhang