Objective: To investigate the effect of vortioxetine and mirtazapine on levodopa-induced dyskinesia (LID) in a rat model of Parkinson’s disease (PD), we analyzed abnormal involuntary movements (AIMs) in hemiparkinsonian rats with co-administration of levodopa with vortioxetine or mirtazapine.

Background: Non-dopaminergic neurotransmitters, such as serotonin, adenosine, endocannabinoid, and glutamate, have been emphasized on the pathophysiology of LID in PD. We have previously reported [1] that intermittent levodopa treatment on unilateral PD model rats developed LID, and rats with co-administration of zonisamide ameliorated the development of LID via downregulation of striatal mRNAs, such as adenosine A2A receptor, cannabinoid CB1 receptor. Furthermore, we reported [2] that the severity of LID was correlated with the ratio of serotonin 5HT1B to 5HT1A receptor mRNA expression in the lesioned striatum.

Method: PD model rats made by 6-OHDA injection into the unilateral medial forebrain bundle were subdivided into three groups as follows; 1) no medication (Group N), 2) intermittent levodopa injection (12 mg/kg plus benserazide 4mg/kg, once daily) (Group I), 3) intermittent levodopa (the same as above) and vortioxetine (5 mg/kg, once daily) injections (Group IV5), and 4) intermittent levodopa (the same as above) and mirtazapine (10 mg/kg, once daily) injections (Group IM10). After two weeks of treatments, we analyzed axial, limb, and orolingual AIMs and compared in groups.

Results: Rats in group IV5 and IM10 had reduced axial, limb, and orolingual AIM scores compared with rats in group I.Furthermore, rats in group IM10 showed low scores of orolingual AIM compared with groups I and IV5.

Conclusion: Vortioxetine and mirtazapine may have favorable effects on LID in a rat model of PD.

References: [1] Oki M, Kaneko S, Morise S, Takenouchi N, Hashizume T, Tsuge A, Nakamura M, Wate R, Kusaka H. Zonisamide ameliorates levodopa-induced dyskinesia and reduces expression of striatal genes in Parkinson model rats. Neurosci Res 122:45-50, 2017.
[2] Tohge R, Kaneko S, Morise S, Oki M, Takenouchi N, Murakami A, Nakamura M, Kusaka H, Yakushiji Y. Zonisamide attenuates the severity of levodopa-induced dyskinesia via modulation of the striatal serotonergic system in a rat model of Parkinson’s disease. Neuropharmacology 198:108771, 2021.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-effect-of-vortioxetine-and-mirtazapine-on-levodopa-induced-dyskinesia-in-a-rat-model-of-parkinsons-disease/