The nonsteroidal antiinflammatory drug piroxicam reverses the onset of depressive-like behavior in 6-OHDA animal model of Parkinson's disease

- The infusion of 6-OHDA was able to promote a depressive-like behavior in rats.
- 6-OHDA-lesioned rats exhibited a reduction in the levels of hippocampal serotonin.
- Animals treated with piroxicam did not show depressive-like behavior.
- Piroxicam was able to prevent the reduction in hippocampal serotonin.

Depression is one of the most common psychiatric symptoms in patients with Parkinson's disease (PD). Some authors have reported that depression is characterized by activation of the inflammatory response. Animal models of PD also present with depressive-like behavior, such as increased immobility time in the modified forced swim test and anhedonia-like behavior in the sucrose preference test. Considering the potential neuroprotective effect of nonsteroidal antiinflammatory drugs in neurodegenerative diseases, the objective of the present study was to investigate the effects of piroxicam on depressive-like behavior in male Wistar rats lesioned with 6-hydroxydopamine (6-OHDA) in the substantia nigra (SN). Antidepressant-like effects were observed after prolonged administration of piroxicam for 21 days. In the forced swim test, the 6-OHDA + saline group exhibited significant reductions in swimming time and increased immobility time compared with the sham + saline. In the sucrose preference test, the 6-OHDA + piroxicam group exhibited no reduction of sucrose preference compared with the sham + saline, with significant effects of treatment and time and a significant treatment × time interaction. 5-Hydroxytryptamine (5-HT) levels significantly decreased in the hippocampus in the 6-OHDA + saline group and not changed in the 6-OHDA + piroxicam group when compared with the sham + saline on day 21. In conclusion, 21-day treatment with piroxicam reversed the onset of depressive-like behavior and prevented the reduction of hippocampal 5-HT levels.