The pro-depressive effect of levodopa in a 6-OHDA-induced hemiparkinsonism rat model

Abstract

Rationale: Treatment of Parkinson's disease has been by now symptomatic. The literature on the efficacy and side effects of levodopa has been contradictory. Some authors mention an anti-depressant effect of the agent, while others believe that it is exactly levodopa that eventually induces the occurrence of depressive symptoms.Aim: To reproduce the OHDA-hemiparkinsonism rat model with subsequent assessment of both external and structural manifestations of the disorder, as well as to study the efficacy of levodopa for motor and non-motor symptoms of parkinsonism.Materials and methods: The study was performed in 52 male Wistar rats. The disease model included stereotaxic administration of neurotoxic 6-OHDA into the pars compacta of the substantia nigra. At 2 months after the administration, the animals underwent test for motor (Rotarod, cylinder, ketamine-induced rotation in the rotometer) and non-motor abnormalities (open field, social interest, conditioned escape response).Results: In 18% of the animals no hemiparkinsonism symptoms were found. 32% of rats had only motor symptoms, whereas in 50% of the animals both motor and non-motor symptoms were noted. Levodopa could partially correct the motor abnormalities, with augmentation of depressive-like behavior.Conclusion: Levodopa has shown its partial efficacy in correction of the motor symptoms caused by administration of 6-OHDA neurotoxin; however, it caused such side effects as augmentation of depressive-like behavior and anxiety.