Peterlik, Daniel and Stangl, Christina and Bauer, Amelie and Bludau, Anna and Keller, Jana and Grabski, Dominik and Killian, Tobias and Schmidt, Dominic and Zajicek, Franziska and Jaeschke, Georg and Lindemann, Lothar and Reber, Stefan O. and Flor, Peter J. and Uschold-Schmidt, Nicole (2017) Blocking metabotropic glutamate receptor subtype 5 relieves maladaptive chronic stress consequences. BRAIN BEHAVIOR AND IMMUNITY, 59. pp. 79-92. ISSN 0889-1591, 1090-2139
Full text not available from this repository. (Request a copy)Abstract
Etiology and pharmacotherapy of stress-related psychiatric conditions and somatoform disorders are areas of high unmet medical need. Stressors holding chronic plus psychosocial components thereby bear the highest health risk. Although the metabotropic glutamate receptor subtype 5 (mGlu5) is well studied in the context of acute stress-induced behaviors and physiology, virtually nothing is known about its potential involvement in chronic psychosocial stress. Using the mGlu5 negative allosteric modulator CTEP (2-chloro-4[2-[2,5-dimethy1-1-[4-(trifluoromethoxy)phenylilmidazol-4yl]ethynyl]pyridine), a close analogue of the clinically active drug basimglurant- but optimized for rodent studies, as well as mGlu5-deficient mice in combination with a mouse model of male subordination (termed CSC, chronic subordinate colony housing), we demonstrate that mGlu5 mediates multiple physiological, immunological, and behavioral consequences of chronic psychosocial stressor exposure. For instance, CTEP dose dependently relieved hypothalamo-pituitary-adrenal axis dysfunctions, colonic inflammation as well as the CSC-induced increase in innate anxiety; genetic ablation of mGlu5 in mice largely reproduced the stress-protective effects of CTEP and additionally ameliorated CSC-induced physiological anxiety. Interestingly, CSC also induced an upregulation of mGlu5 in the hippocampus, a stress-regulating brain area. Taken together, our findings provide evidence that mGlu5 is an important mediator for a wide range of chronic psychosocial stress-induced alterations and a potentially valuable drug target for the treatment of chronic stress-related pathologies in man. (C) 2016 Elsevier Inc. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHRONIC PSYCHOSOCIAL STRESS; NEGATIVE ALLOSTERIC MODULATOR; MAJOR DEPRESSIVE DISORDER; MALE-MICE; PSYCHOLOGICAL STRESS; MGLU5 RECEPTORS; PRENATAL STRESS; MOOD DISORDERS; ANIMAL-MODEL; ENTERIC GLIA; mGlu5; Knockout; CTEP; Chronic subordinate colony housing; Chronic psychosocial stress; Stress-protective phenotype |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Biology, Preclinical Medicine > Institut für Zoologie > Molecular and Cellular Neurobiology (Prof. Dr. Peter J. Flor) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 12:58 |
| Last Modified: | 19 Feb 2019 09:20 |
| URI: | https://pred.uni-regensburg.de/id/eprint/151 |
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