Abstract
Continuous dopaminergic treatment is considered to prevent or delay the occurrence of dyskinesia in patients with Parkinson’s disease (PD). Rotigotine is a non-ergolinic D3 > D2 > D1 dopamine-receptor agonist for the treatment of PD using a transdermal delivery system providing stable plasma levels. We aimed to investigate the differential influence on gene expression of pulsatile l-DOPA or rotigotine versus a continuous rotigotine treatment. The gene expression profile within the nigro-striatal system of unilateral 6-hydroxydopamine-lesioned rats was assessed in order to differentiate potential changes in gene expression following the various treatment using Affymetrix microarrays and quantitative RT-PCR. The expression of 15 genes in the substantia nigra and of 11 genes in the striatum was altered under pulsatile treatments inducing dyskinetic motor response, but was unchanged under continuous rotigotine treatment that did not cause dyskinetic motor response. The route of administration of a dopaminergic drug is important for the induction or prevention of motor abnormalities and adaptive gene expressions. The decline of neurotrophin-3 expression under pulsatile administration was considered of particular importance.
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Acknowledgments
The authors thank for the help in the analysis of the Gene Chip Affymetrix arrays by Dr. Susanne Kneitz. And a special thank for devoted technical work provided by Ms. Miryame Hofmann. The study was sponsored by SCHWARZ BIOSCIENCES, Alfred-Nobel Strasse 10, 40789, Monheim, Germany.
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Grünblatt, E., Schmidt, W.J., Scheller, D.K.A. et al. Transcriptional alterations under continuous or pulsatile dopaminergic treatment in dyskinetic rats. J Neural Transm 118, 1717–1725 (2011). https://doi.org/10.1007/s00702-010-0552-y
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DOI: https://doi.org/10.1007/s00702-010-0552-y