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Anti‐stress effects of combined block of glucocorticoid and mineralocorticoid receptors in the paraventricular nucleus of the hypothalamus
Author(s) -
Ding Hui,
Cui SuYing,
Cui XiangYu,
Liu YuTong,
Hu Xiao,
Zhao HuiLing,
Qin Yu,
Kurban Nurhumar,
Zhang YongHe
Publication year - 2021
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.15511
Subject(s) - endocrinology , medicine , mineralocorticoid receptor , glucocorticoid receptor , mineralocorticoid , corticosterone , hypothalamus , behavioural despair test , antagonist , spironolactone , glucocorticoid , corticotropin releasing hormone , elevated plus maze , psychology , receptor , anxiety , hippocampus , hormone , antidepressant , aldosterone , psychiatry
Background and Purpose Mineralocorticoid receptors (MRs), glucocorticoid receptors (GRs) and corticotropin‐releasing factor (CRF) in the paraventricular nucleus of hypothalamus (PVN) are involved in the response to stress. The present study investigated the role of GRs and MRs in the PVN in regulating depressive and anxiety‐like behaviours. Experimental Approach 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 of corticosterone treatment. Behavioural tests were run on days 22 and 23. Depressive‐ and anxiety‐like behaviours 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 Rats exposed to corticosterone exhibited depressive‐ and anxiety‐like behaviours. 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 behaviours. The spironolactone‐treated group exhibited an increase in MRs without influencing GRs and CRF in the PVN and improved anxiety‐like behaviours. Interestingly, the intra‐PVN administration of RU486 and spironolactone combined restored expression of GRs, MRs and CRF and improved depressive‐ and anxiety‐like behaviours. Conclusion and Implications In this rat model of stress, the simultaneous restoration of GRs, MRs and CRF in the PVN might play an important role in the treatment of depression and anxiety.