Celecoxib Ameliorates Chronic Restraint Stress-Induced Depression-Like Behavior in Sprague-Dawley Rats.

INTRODUCTION: Chronic stress is associated with depressive-like behaviors, dysregulation of the hypothalamic-pituitary-adrenal axis, and changes in inflammatory signaling. Celecoxib is a selective cyclooxygenase-2 inhibitor that has been investigated as a potential adjunctive treatment for depression; however, its effects in a chronic restraint stress model require further characterization. METHODS: Male Sprague-Dawley rats were randomly assigned to a control group, chronic restraint stress (CRS) model group, CRS plus celecoxib group, or CRS plus fluoxetine group. The CRS procedure was conducted for 6 weeks, with restraint applied for 4 h per day. Celecoxib was administered by oral gavage at a dose of 20 mg/kg/day, and fluoxetine was administered at 10 mg/kg/day for 2 weeks throughout the CRS procedure. Depression-like and related behavioral changes were evaluated using the open field test, forced swimming test, Y-maze test, and sucrose preference test. Cytokine and corticosterone concentrations were measured in hippocampal homogenates. Hippocampal IBA-1 immunoreactivity and histological changes were evaluated using immunofluorescence, H&E staining, Nissl staining, and transmission electron microscopy. RESULTS: Compared with control rats, CRS-exposed rats showed changes in open-field activity, forced-swimming behavior, Y-maze performance, and sucrose preference. Celecoxib treatment was associated with improved behavioral parameters compared with the CRS model group. Celecoxib was also associated with lower concentrations of IL-1β, IL-6, TNF-α, and corticosterone, reduced hippocampal IBA-1 immunoreactivity, and less pronounced histological and ultrastructural alterations. DISCUSSION: These findings indicate that celecoxib was associated with improved behavioral outcomes and reduced inflammatory, endocrine, histological, and ultrastructural alterations in CRS-exposed rats.