title: L-dopa-induced dyskinesia: beyond an excessive dopamine tone in the striatum.
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.
authors.affiliation: 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.
authors.forename: Gregory
authors.initials: G
authors.lastname: Porras
authors.affiliation: 1] Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France [2] CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: De Deurwaerdere
authors.affiliation: 1] Motac neuroscience, Manchester, UK [2] Institute of Laboratory Animal Sciences, China Academy of Medical Sciences, Beijing, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Life Sciences and Biotechnology (SVeB), University of Ferrara, Ferrara, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Marti
authors.affiliation: Institute of Pharmacology and Toxicology, Charité Campus Mitte, Humboldt University, 10117 Berlin, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Morgenstern
authors.affiliation: Institute of Pharmacology and Toxicology, Charité Campus Mitte, Humboldt University, 10117 Berlin, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Sohr
authors.affiliation: 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.
authors.forename: Erwan
authors.initials: E
authors.lastname: Bezard
authors.affiliation: Department of Medical Sciences, Section of Pharmacology, University of Ferrara, Ferrara, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Morari
authors.affiliation: 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.
authors.forename: Wassilios G
authors.initials: WG
authors.lastname: Meissner
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects; D000818:Animals; D001545:Benserazide / Q000009:adverse effects / Q000493:pharmacokinetics; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000009:adverse effects* / Q000493:pharmacokinetics; D004338:Drug Combinations; D020820:Dyskinesias / Q000209:etiology* / Q000378:metabolism; D005260:Female; D007980:Levodopa / Q000009:adverse effects* / Q000493:pharmacokinetics; D008253:Macaca mulatta; D008297:Male; D010300:Parkinson Disease / Q000378:metabolism
chemical_list: D015259:Dopamine Agents; D004338:Drug Combinations; C005177:benserazide, levodopa drug combination; D007980:Levodopa; D001545:Benserazide; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine