Session Information
Date: Wednesday, September 25, 2019
Session Title: Physiology and Pathophysiology
Session Time: 1:15pm-2:45pm
Location: Les Muses, Level 3
Objective: To investigate the change of striatal serotonergic system according to the administration of levodopa and zonisamide (ZNS) on the striatal serotonergic system, we analyzed the striatal serotonin transporter (SERT) expression in the difference of antiparkinsonian treatments in a rat model of Parkinson’s disease (PD).
Background: Non-dopaminergic neurotransmitters, such as serotonin and adenosine, have been emphasized on the pathophysiology of Parkinson’s disease (PD). We have previously reported [1] that intermittent levodopa treatment on unilateral PD model rats developed LID. Whilst, co-administration of ZNS ameliorated the development of LID via amelioration of enhanced A2A receptors expression.
Method: PD model rats made by 6-OHDA injection into the unilateral medial forebrain bundle were subdivided into three groups and treated as follows; 1) no medication (group N), 2) intermittent levodopa injection (12 mg/kg plus benserazide 4mg/kg, twice daily) (group I) and 3) intermittent levodopa and zonisamide (26 mg/kg, twice daily) (ZNS) injections (group IZ). Two weeks after the treatment, striatal SERT expression was quantitated by immunohistochemistry and compared between lesioned and intact sides.
Results: The ratio of striatal SERT expression (lesioned side /intact side) was significantly elevated in group N. The enhanced ratio of that was reduced in group I. Further reduction of the ratio was observed in group IZ.
Conclusion: Up-regulation of serotonin transporter may be compensation for dopaminergic deficit. ZNS may have an anti-dyskinetis effect via reduction of the striatal serotonergicinnervation in the 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.
To cite this abstract in AMA style:
R. Tohge, S. Kaneko, S. Morise, M. Oki, M. Nakamura, N. Takenouchi, H. Kusaka. Co-administration of levodopa and zonisamide reduces the serotonin transporter expression in a rat model of Parkinson’s disease [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/co-administration-of-levodopa-and-zonisamide-reduces-the-serotonin-transporter-expression-in-a-rat-model-of-parkinsons-disease/. Accessed May 15, 2025.« Back to 2019 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/co-administration-of-levodopa-and-zonisamide-reduces-the-serotonin-transporter-expression-in-a-rat-model-of-parkinsons-disease/