Abstract
Parkinson's disease is a progressive debilitative neurodegenerative disease characterised mostly with bradykinesia, tremor, catatonia, drooping posture, unsteady gate and unstable steps. Levodopa has been proven to be among the most effective and acceptable treatment that can reconstitute dopamine in Parkinson's disease. However, there is a relation between levodopa long term administration and dyskinesia. Regarding the effectiveness of ondansetron in Parkinson's disease, we planned to test its effect on levodopa-induced dyskinesia (LID). In this study, Parkinsonism was induced in 40 adult male rats using 6-OHDA injection into the striatum via stereotaxic surgery. After 2 weeks, all animals tested for Parkinson's disease using apomorphine rotation test. Then, animals with positive symptoms for Parkinsonism divided into 4 equal groups, the first group treated with levodopa 50 mg/kg i.p, the second group received only distilled water, the third and forth groups treated with levodopa 50 mg/kg i.p plus two different doses of ondansetron (0.04 and 0.08 mg/kg i.p) for 3 weeks. Animals tested for dyskinesia using AIMs and rotarod tests at specific days and a week after discontinuation of ondansetron. Evaluations of AIMs test showed significant changes in dyskinetic movements and reduction in scores in groups treating with ondansetron when compared with the first group. Upon discontinuations of ondansetron in the last two groups, AIMs scores significantly increased. While in rotarod test, ondansetron had no additional benefit when added to levodopa in motor coordination of animals. Findings of this study suggest that co administration of ondansetron with levodopa is effective in attenuating dyskinesia.
Highlights
During long term treatment of Parkinson's disease (PD) with Levodopa, serious dyskinetic movements have been reported that is known as Levodopa-induced dyskinesia (LID)
The results showed that in the first group on day 9, Abnormal involuntary movements (AIMs) scores increased significantly compared to the control group (P < 0.01) indicating that dyskinesia has occurred (Fig. 2)
We observed that early treatment with levodopa at 50 mg/kg could increase AIMs scores; the test that is normally use for dyskinetic measurements in animals
Summary
During long term treatment of Parkinson's disease (PD) with Levodopa, serious dyskinetic movements have been reported that is known as Levodopa-induced dyskinesia (LID). The management of LID is a challenging issue. It has serious negative effects on the quality of the patient’s life and limits the use of levodopa that is the most effective drug for control of the disease (Guridi et al, 2012). In the last few decades, research interest has been focused on medications that could provide more continuous dopaminergic stimulation (Yang et al, 2012). This strategy was not successful and the control of LID remained an unsolved problem. It is proposed that inhibition of some subtype receptors of serotonin like 5-HT2 A/2C, 5-HT3 and 5-HT6 can improve extrapyramidal disorders (Ohno et al, 2015)
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