L-dopa-induced dyskinesia: beyond an excessive dopamine tone in the striatum

Gregory Porras; Philippe De Deurwaerdere; Qin Li; Matteo Marti; Rudolf Morgenstern; Reinhard Sohr; Erwan Bezard; Michele Morari; Wassilios G Meissner

doi:10.1038/srep03730

L-dopa-induced dyskinesia: beyond an excessive dopamine tone in the striatum

Sci Rep. 2014 Jan 16:4:3730. doi: 10.1038/srep03730.

Authors

Gregory Porras¹, Philippe De Deurwaerdere², Qin Li³, Matteo Marti⁴, Rudolf Morgenstern⁵, Reinhard Sohr⁵, Erwan Bezard⁶, Michele Morari⁷, Wassilios G Meissner⁸

Affiliations

¹ 1] Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France [2] CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France [3] Motac neuroscience, Manchester, UK.
² 1] Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France [2] CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France.
³ 1] Motac neuroscience, Manchester, UK [2] Institute of Laboratory Animal Sciences, China Academy of Medical Sciences, Beijing, China.
⁴ Department of Life Sciences and Biotechnology (SVeB), University of Ferrara, Ferrara, Italy.
⁵ Institute of Pharmacology and Toxicology, Charité Campus Mitte, Humboldt University, 10117 Berlin, Germany.
⁶ 1] Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France [2] CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France [3] Motac neuroscience, Manchester, UK [4] Institute of Laboratory Animal Sciences, China Academy of Medical Sciences, Beijing, China [5] Service de Neurologie, Centre Expert Parkinson, CHU de Bordeaux, 33076 Bordeaux, France.
⁷ Department of Medical Sciences, Section of Pharmacology, University of Ferrara, Ferrara, Italy.
⁸ 1] Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France [2] CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France [3] Service de Neurologie, Centre Expert Parkinson, CHU de Bordeaux, 33076 Bordeaux, France [4] Centre de référence AMS, CHU de Bordeaux, 33076 Bordeaux, France.

Abstract

L-dopa remains the mainstay treatment for Parkinson's disease (PD), although in later stages, treatment is complicated by L-dopa-induced dyskinesias (LID). Current evidence links LID to excessive striatal L-dopa-derived dopamine (DA) release, while the possibility of a direct involvement of L-dopa itself in LID has been largely ignored. Here we show that L-dopa can alter basal ganglia activity and produce LID without enhancing striatal DA release in parkinsonian non-human primates. These data may have therapeutic implications for the management of advanced PD since they suggest that LID could result from diverse mechanisms of action of L-dopa.

MeSH terms

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / adverse effects
Animals
Benserazide / adverse effects
Benserazide / pharmacokinetics
Corpus Striatum / drug effects
Corpus Striatum / metabolism
Disease Models, Animal
Dopamine / metabolism
Dopamine Agents / adverse effects*
Dopamine Agents / pharmacokinetics
Drug Combinations
Dyskinesias / etiology*
Dyskinesias / metabolism
Female
Levodopa / adverse effects*
Levodopa / pharmacokinetics
Macaca mulatta
Male
Parkinson Disease / metabolism

Substances

Dopamine Agents
Drug Combinations
benserazide, levodopa drug combination
Levodopa
Benserazide
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Dopamine