Duloxetine increases the effects of levodopa in a rat model of Parkinson's disease

Abstract

Background: In patients with advanced Parkinson's disease, serotonergic and noradrenergic systems act as surrogates for the failing dopaminergic system. Treatment with a serotonin–noradrenaline reuptake inhibitor might help maintain levodopa-derived dopamine levels in the dopamine-denervated striatum. However, clinical utility of a serotonin–noradrenaline reuptake inhibitor for treatment of motor symptoms in Parkinson's disease is not yet clear. Aim: To investigate whether pretreatment with duloxetine, one of the serotonin–noradrenaline reuptake inhibitors, has any impact on the effects of levodopa in a rat model of Parkinson's disease. Methods: We used 6-hydroxydopamine-lesioned hemiparkinsonian rats. One group received duloxetine for 5 days and the other group received the same dose of saline. Levodopa was injected into each rat 6 h after the last administration of duloxetine or saline. An abnormal involuntary movement score was measured every 20 min during the 3-h period after the injection of levodopa. Results: Levodopa-induced abnormal involuntary movement was significantly enhanced in duloxetine-treated rats when compared with saline-treated rats. Conclusion: Duloxetine appears to increase the effects of levodopa in a rat model of Parkinson's disease, although it might increase the risk of levodopa-induced dyskinesia.