Anti‐stress effects of combined block of glucocorticoid and mineralocorticoid receptors in the paraventricular nucleus of the hypothalamus
| Autor: | Xiao Hu, Hui Ding, Su-Ying Cui, Yu Qin, Nurhumar Kurban, Yong-He Zhang, Hui-Ling Zhao, Xiang-Yu Cui, Yu-Tong Liu |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
endocrine system medicine.medical_specialty Corticotropin-Releasing Hormone medicine.drug_class Hypothalamus 03 medical and health sciences chemistry.chemical_compound Receptors Glucocorticoid 0302 clinical medicine Mineralocorticoid receptor Glucocorticoid receptor Corticosterone Internal medicine Animals Medicine Chronic stress Glucocorticoids Pharmacology business.industry fungi Rats Receptors Mineralocorticoid 030104 developmental biology Endocrinology nervous system chemistry Paraventricular nucleus of hypothalamus Mineralocorticoid business hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery Glucocorticoid Paraventricular Hypothalamic Nucleus medicine.drug |
| Zdroj: | British Journal of Pharmacology. 178:3696-3707 |
| ISSN: | 1476-5381 0007-1188 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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