The study to evaluate the antidepressant effect of Probenecid and Allopurinol in Swiss albino mice and it’s comparison with imipramine using forced swim test

Abstract

Background: Depression is a prevalent psychiatric disorder with multi factorial
origins, including neurochemical imbalances and oxidative stress. Current
antidepressants have limitations in efficacy, onset of action, and side-effect profiles,
prompting the need for novel therapeutics approaches.
Objective: This study aimed to evaluate the potential antidepressant effects of
Probenecid and Allopurimol, both xanthine oxidase inhibitors, in Swiss albino mice,
and to compare their efficacy with Imipramine, a standard antidepressant, using the
Forced Swim Test (FST).
Methods: A total of 24 male Swiss albino mice were randomly assigned to four
Groups: control (saline), Probenecid (200 mg/kg), Allopurinal (200 mg/kg), and
Imipramine (10 mg/kg). The FST was conducted on days 1, 10, 20, and 30, and the
duration of immobility was recorded as an index of depressive behavior. A decrease
in immobility time indicates antidepressant activity.
Results: No significant differences in immobility duration were observed among the
groups on days 1 and 10. However, significant reductions were noted on days 20 and
30 in the Probenecid, Allopurinol, and Imipramine groups compared to the control.
The antidepressant effect was most pronounced in the Imipramine group, but both
Probenecid and Allopurinol also demonstrated substantial efficacy, with statistically
significant decreases in immobility time from baseline. The data suggest a role for
oxidative stress modulation in depression and support the involvement of xanthine
oxidase inhibition.
Conclusion: Probenecid and Allopurinol exhibit significant antidepressant-like
effects in mice, comparable to imipramine. These findings highlight the potential of
xanthine oxidase inhibitors as promising candidates for the treatment of depression,
likely through mechanisms involving oxidative stress reduction and serotonin
metabolism enhancement.