Antidepressant-like effects of the xanthine oxidase enzyme inhibitor allopurinol in rats. A comparison with fluoxetine

• Allopurinol and fluoxetine had similar antidepressant efficacies when administered separately.
• Combined administration of allopurinol and fluoxetine did not decrease the duration of immobility.
• Allopurinol alone or combined with fluoxetine treatment caused an increase in blood serotonin levels.
• The amount of time spent swimming increased in the fluoxetine, allopurinol and fluoxetine + allopurinol groups in the forced swimming test.

Allopurinol is a xanthine oxidase enzyme inhibitor that is widely used for the treatment of hyperuricemia and gout. The activity of tryptophan 2,3-dioxygenase, which metabolizes tryptophan (TRP), is decreased by xanthine oxidase inhibitors, causing TRP levels in the body to be increased. Increases in TRP levels in the brain might have antidepressant effects. The purpose of this study is to evaluate the antidepressant effects of allopurinol compared to those of fluoxetine, which is a proven antidepressant. Thirty-two Wistar albino male rats were divided into four groups (control, 10 mg/kg fluoxetine, 50 mg/kg allopurinol, 50 mg/kg allopurinol + 10 mg/kg fluoxetine; n = 8 per group), and forced swimming tests were performed before and after 14 days of drug administration. Serotonin, 5-hydroxyindolacetic acid and uric acid levels were measured in blood samples after the final treatment. When allopurinol and fluoxetine were administered separately, a decrease in the duration of immobility and an increased duration of swimming were observed in the forced swimming test. The results showed similar antidepressant efficacies between allopurinol and fluoxetine. However, we found no statistically significant difference in the antidepressant effect of the combined therapy versus single drug therapy.