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Anti-stress effects of combined glucocorticoid and mineralocorticoid receptor blockade in the paraventricular nucleus of the hypothalamus
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  • Hui Ding,
  • Xiang-Yu Cui,
  • Yu-Tong Liu,
  • Su-Ying Cui,
  • Xiao Hu,
  • Hui-Ling Zhao,
  • Yu Qin,
  • Nurhumar Kurban,
  • Yong-He Zhnag
Hui Ding
Peking University Health Science Centre
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Xiang-Yu Cui
Peking University Health Science Centre
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Yu-Tong Liu
Peking University Health Science Centre
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Su-Ying Cui
Peking University Health Science Centre
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Xiao Hu
Peking University Health Science Centre
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Hui-Ling Zhao
Peking University Health Science Centre
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Yu Qin
Peking University Health Science Centre
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Nurhumar Kurban
Peking University Health Science Centre
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Yong-He Zhnag
Peking University Health Science Centre
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Abstract

Background and Purpose: Mineralocorticoid receptors (MRs), glucocorticoid receptors (GRs) and corticotropin-releasing factor (CRF) in the paraventricular nucleus of the hypothalamus (PVN) are implicated in the stress response. The present study investigated the role of GRs and MRs in the PVN in regulating depressive and anxiety-like behaviors. Experimental Approach: To model chronic stress, rats were exposed to chronic corticosterone treatment via drinking water for 21 days, and the GR antagonist RU486 and MR antagonist spironolactone, alone and combined, were directly injected in the PVN daily for 7 days before the behavioral tests. 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. Key Results: 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. Conclusion and Implications: 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.

Peer review status:IN REVISION

20 Jul 2020Submitted to British Journal of Pharmacology
22 Jul 2020Assigned to Editor
22 Jul 2020Submission Checks Completed
27 Jul 2020Editorial Decision: Revise Minor
04 Sep 20201st Revision Received
06 Sep 2020Submission Checks Completed
06 Sep 2020Assigned to Editor
10 Sep 2020Editorial Decision: Revise Minor