# Targeting COX-2 to Alleviate Depressive Phenotypes: Etoricoxib’s Antidepressant Effects in Chronic Unpredictable Mild Stress-Exposed Mice

## TL;DR

This study shows that etoricoxib, a COX-2 inhibitor, reduces depressive behaviors in mice exposed to chronic stress, suggesting it may have antidepressant effects.

## Contribution

The study demonstrates etoricoxib's novel antidepressant-like effects in a chronic stress mouse model.

## Key findings

- Etoricoxib significantly reduced immobility in the Forced Swim Test compared to the CUMS control group.
- Etoricoxib increased sucrose preference in stressed mice, indicating improved anhedonia.
- Both doses of etoricoxib (3 mg/kg and 9 mg/kg) showed significant antidepressant-like effects.

## Abstract

The current study evaluated the antidepressant effect of etoricoxib, a well-established non-steroidal anti-inflammatory drug, in the chronic unpredictable mild stress (CUMS) model of depression in Swiss albino mice. The mice were exposed to CUMS for 42 days by using a variety of stressors. A total of 54 Swiss albino mice of either sex were used for the study, which were tested for locomotor activity using the Open Field Test (OFT). The mice were randomly divided into four groups, each with six animals, which were used to evaluate the antidepressant effect of etoricoxib using the Forced Swim Test (FST). For the prolonged experiment, the remaining 30 mice were used to evaluate the antidepressant effect using the chronic mild stress model (CMS), followed by a sucrose preference test (SPT) for six weeks. Treatment with etoricoxib at any of the doses (3 mg/kg and 9 mg/kg, PO) and the positive control, fluoxetine, significantly reversed these behavioral changes as compared to the CUMS using the OFT. The etoricoxib at 3 mg/kg and 9 mg/kg doses administered to stressed animals produced a significant (p < 0.05 and 𝑝 < 0.001) decrease in the duration of immobility when compared with CUMS control group. The test drug etoricoxib (3 mg/kg and 9 mg/kg) significantly (p < 0.001) increased the sucrose preference at week 6 when compared to the stress group. To conclude, the present study suggested that etoricoxib exerts an antidepressant-like effect in mice exposed to CUMS by reducing the symptoms of depression based on behavioural tests.