Clotrimazole ameliorates chronic mild stress-induced depressive-like behavior in rats; crosstalk between the HPA, NLRP3 inflammasome, and Wnt/ β-catenin pathways

Int Immunopharmacol. 2023 Dec 15;127:111354. doi: 10.1016/j.intimp.2023.111354. Online ahead of print.ABSTRACTDepression is a major emotional disorder that has a detrimental effect on quality of life. The chronic mild stress (CMS)-depression model was adopted in rats to evaluate the neurotherapeutic effect of Clotrimazole (CLO) and investigate the possible mechanisms of its antidepressant action via its impact on the hypothalamic pituitary adrenal (HPA) axis and the stress hormone, cortisol. It was found that azole antifungals affect steroidogenesis and the HPA axis. Behavioral, histopathological, inflammatory, and apoptotic pathways were assessed. Serum cortisol, inflammasome biomarkers, hippocampal NLRP3, caspase-1, and IL-18, and the canonical Wnt/β-catenin neurogenesis biomarkers, Wnt3a, and non-phosphorylated β-catenin levels were also determined. Different stressors were applied for 28 days to produce depressive-like symptoms, and CLO was administered at a daily dose of 30 mg/kg body weight. Subsequently, behavioral and biochemical tests were carried out to assess the depressive-like phenotype in rats. Stressed rats showed increased immobility time in the forced swimming test (FST), decreased grooming time in the splash test (ST), increased serum cortisol levels, increased inflammasome biomarkers, and decreased neurogenesis. However, administration of CLO produced significant antidepressant-like effects in rats, which were accompanied by a significant decrease in immo...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Source Type: research