Chronic Quetiapine Administration Has a Therapeutic Effect on Anxiety and Depression‐Like Behavior in a Chronic Unpredictable Mild Stress (CUMS) Rat Model

Background The mechanisms underlying quetiapine's effects on anxiety‐ and depression‐like behaviors induced by chronic unpredictable mild stress (CUMS) remain unclear. This study aimed to evaluate the therapeutic potential of quetiapine in a rat model of CUMS. Materials and Methods In the first experiment, 40 adult female Wistar albino rats were randomly assigned to either a control group (non‐stressed, n = 20) or a chronic unpredictable mild stress (CUMS) group ( n = 20) for 28 consecutive days. To evaluate stress‐related behavioral changes, the sucrose preference test (SPT), fecal boli count, and elevated plus maze (EPM) test were conducted on days 29 and 30. In the second experiment, on day 30, animals from both initial groups were further divided into four experimental groups ( n = 10 per group): (1) Control (1 mL saline, i.p., for 30 days), (2) Quetiapine (QET; 10 mg/kg/day, i.p., for 30 days), (3) CUMS only (no treatment), and (4) CUMS + QET (10 mg/kg/day, i.p., for 30 days). Following treatment, behavioral assessments (SPT, forced swim test (FST), elevated plus maze test (EPM), and fecal boli count) were conducted on days 61, 62, and 63. Results CUMS induced significant anxiety‐ and depression‐like behaviors. Chronic quetiapine administration (10 mg/kg/day) reversed these behavioral deficits, suggesting antidepressant and anxiolytic effects. Conclusion Quetiapine alleviates CUMS‐induced anxiety and depression‐like behaviors, supporting its potential as both monotherapy and adjunctive treatment in stress‐related disorders. Further research should explore sex differences, dose‐response effects, biochemical or molecular markers, and other stress paradigms to optimize clinical relevance.