The mechanism of antidepressant-like effects of piroxicam in rats

Objective: To investigate the antidepressant-like effect of piroxicam with a focus on serotonergic neurotransmission. Materials and Methods: Rats were randomly distributed into the following groups: 0.9% saline control; 3 mg/kg pizotifen; 10 mg/kg sertraline; 10 mg/kg piroxicam; 10 mg/kg sertraline + 10 mg/kg piroxicam; 10 mg/kg sertraline + 3 mg/kg pizotifen; and 10 mg/kg piroxicam + 3 mg/kg pizotifen. All the drugs were dissolved in 0.9% saline. Three administrations of the drugs (piroxicam and sertraline) were performed 1, 5 and 24 h before testing the animals in the open field followed by the forced swim test (FST). Piroxicam and sertraline were administered orally by gavage and pizotifen was administered intraperitoneally 30 min before gavage. Immediately after the FST, the hippocampi were rapidly dissected for neurochemical analysis in high-performance liquid chromatography. Results: Acute treatment with piroxicam promoted an antidepressant-like effect in the FST, which was associated with an increase in serotonin levels in the hippocampus. This effect was potentiated in the piroxicam + sertraline group but counteracted by administration of the non-selective serotonin receptor antagonist pizotifen. Conclusion: These results suggest that the antidepressant-like effect of piroxicam in the FST is mediated by the serotonin system; however, by different mechanisms from those of sertraline.