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Zonisamide ameliorates levodopa-induced dyskinesia and reduces expression of striatal genes in Parkinson model rats.
- Source :
-
Neuroscience research [Neurosci Res] 2017 Sep; Vol. 122, pp. 45-50. Date of Electronic Publication: 2017 May 31. - Publication Year :
- 2017
-
Abstract
- To investigate the difference in results according to the mode of levodopa administration and the effect of zonisamide (ZNS), we analyzed the mRNA expression of dopaminergic and non-dopaminergic receptors in the striatum of Parkinson model rats in relation to the development of levodopa-induced dyskinesia (LID). Unilateral Parkinson model rats were subdivided into 4 groups and treated as follows: no medication (group N), continuous levodopa infusion (group C), intermittent levodopa injection (group I), and intermittent levodopa and ZNS injection (group Z). Two weeks after the treatment, LID was observed in group I and Z, but less severe in group Z. The level of both D1 and D2 receptor mRNAs was elevated in groups I and Z, but only D2 receptor mRNA expression was elevated in group C. Adenosine A2A receptor mRNA showed increased expression only in group I. The level of endocannabinoid CB1 receptor mRNA was elevated in groups N, C, and I, but not in group Z. Intermittent injection of levodopa caused LID, in association with elevated expression of D1 and A2A receptors. ZNS ameliorated the development of LID and inhibited up-regulation of A2A and CB1 receptors. Modulation of these receptors may lead to therapeutic approaches for dyskinesia.<br /> (Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.)
- Subjects :
- Animals
Anticonvulsants administration & dosage
Dopamine Agents administration & dosage
Dopamine Agents adverse effects
Dyskinesia, Drug-Induced metabolism
Female
Isoxazoles administration & dosage
Levodopa administration & dosage
Levodopa adverse effects
Rats
Rats, Sprague-Dawley
Zonisamide
Anticonvulsants pharmacology
Corpus Striatum drug effects
Dopamine Agents pharmacology
Dyskinesia, Drug-Induced drug therapy
Gene Expression drug effects
Isoxazoles pharmacology
Levodopa pharmacology
Parkinson Disease drug therapy
Receptor, Adenosine A2A drug effects
Receptor, Cannabinoid, CB1 drug effects
Receptors, Dopamine D1 drug effects
Receptors, Dopamine D2 drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1872-8111
- Volume :
- 122
- Database :
- MEDLINE
- Journal :
- Neuroscience research
- Publication Type :
- Academic Journal
- Accession number :
- 28577977
- Full Text :
- https://doi.org/10.1016/j.neures.2017.04.003