Celecoxib potentiates the antianxiety and anticompulsive-like activity of fluoxetine against chronic unpredictable mild stress in experimental animals.

Obsessive-compulsive disorder (OCD) is considered a heterogeneous anxiety disorder that includes compulsions. Celecoxib is considered an adjuvant to fluoxetine in the management of OCD in a clinical study. However, the experimental evidence is yet to be established. Therefore, the antianxiety and anticompulsive-like activity of celecoxib (20 mg/kg, orally) was evaluated in the presence or absence of fluoxetine (20 mg/kg, orally) in mice who were exposed to chronic unpredictable mild stress (CUMS) for 14 consecutive days. Seven-day treatment of celecoxib significantly attenuated the CUMS-induced anxiety in open-field, hole-board, elevated plus maze tests, and compulsion in the marble-burying test. Celecoxib significantly reversed the CUMS-induced decrease and increase in the levels of serotonin (5-HT) and its metabolite (5-hydroxyindole acetic acid) in the prefrontal cortex, and attenuated the CUMS-induced increase in the levels of inflammatory markers such as interleukin-6 and tumor necrosis factor-α, and apoptosis marker caspase-3 in the prefrontal cortex. Celecoxib also potentiated the anxiolytic, anticompulsive, serotonergic, anti-inflammatory, and antiapoptotic activity of 7-day treatment with fluoxetine in CUMS-challenged animals compared with their monotherapy. Thus, it can be speculated that the combination of an anti-inflammatory agent with selective serotonin reuptake inhibitor could be a better therapeutic option in the management of stress-related disorders including selective serotonin reuptake inhibitor-resistant OCD.