title: Pathophysiology of L-dopa-induced motor and non-motor complications in Parkinson's disease.
abstract: Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa (L-dopa) therapy for Parkinson's disease (PD). L-dopa-induced dyskinesia (LID) are ultimately experienced by the vast majority of patients. In addition, psychiatric conditions often manifested as compulsive behaviours, are emerging as a serious problem in the management of L-dopa therapy. The present review attempts to provide an overview of our current understanding of dyskinesia and other L-dopa-induced dysfunctions, a field that dramatically evolved in the past twenty years. In view of the extensive literature on LID, there appeared a critical need to re-frame the concepts, to highlight the most suitable models, to review the central nervous system (CNS) circuitry that may be involved, and to propose a pathophysiological framework was timely and necessary. An updated review to clarify our understanding of LID and other L-dopa-related side effects was therefore timely and necessary. This review should help in the development of novel therapeutic strategies aimed at preventing the generation of dyskinetic symptoms.
authors.affiliation: Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France.
authors.forename: Matthieu F
authors.initials: MF
authors.lastname: Bastide
authors.affiliation: Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; Department of Neurology, University Hospital Bordeaux, France.
authors.forename: Wassilios G
authors.initials: WG
authors.lastname: Meissner
authors.affiliation: Laboratory of Neurophysiology, Fondazione Santa Lucia, IRCCS, Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Picconi
authors.affiliation: Division of Neuroscience, Institute of Experimental Neurology, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Fasano
authors.affiliation: Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France.
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Fernagut
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Feyder
authors.affiliation: Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Veronica
authors.initials: V
authors.lastname: Francardo
authors.affiliation: Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Cristina
authors.initials: C
authors.lastname: Alcacer
authors.affiliation: Department of Neurology, Columbia University, New York, USA.
authors.forename: Yunmin
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Division of Neuroscience, Institute of Experimental Neurology, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Brambilla
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Fisone
authors.affiliation: Pacific Parkinson's Research Centre and National Parkinson Foundation Centre of Excellence, University of British Columbia, Vancouver, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Jon Stoessl
authors.affiliation: Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Bourdenx
authors.affiliation: Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Engeln
authors.affiliation: Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Navailles
authors.affiliation: Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: De Deurwaerdère
authors.affiliation: Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France.
authors.forename: Wai Kin D
authors.initials: WK
authors.lastname: Ko
authors.affiliation: Department of Biomedical Sciences, Section of Neuropsychopharmacology, Cagliari University, 09124 Cagliari, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Simola
authors.affiliation: Department of Biomedical Sciences, Section of Neuropsychopharmacology, Cagliari University, 09124 Cagliari, Italy.
authors.forename: Micaela
authors.initials: M
authors.lastname: Morelli
authors.affiliation: Univ. de Bordeaux, Institut Interdisciplinaire de neurosciences, UMR 5297, 33000 Bordeaux, France; CNRS, Institut Interdisciplinaire de neurosciences, UMR 5297, 33000 Bordeaux, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Groc
authors.affiliation: Department of Neurology, Hospital Universitario Donostia and Neuroscience Unit, Bio Donostia Research Institute, San Sebastian, Spain.
authors.forename: Maria-Cruz
authors.initials: MC
authors.lastname: Rodriguez
authors.affiliation: Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Eugenia V
authors.initials: EV
authors.lastname: Gurevich
authors.affiliation: Center for Health Sciences, SRI International, CA 94025, USA.
authors.forename: Maryka
authors.initials: M
authors.lastname: Quik
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: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, 20133 Milano, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Mellone
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, 20133 Milano, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Gardoni
authors.affiliation: Department of Biomedical Sciences, Physiology Section, Cagliari University, Cagliari, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Tronci
authors.affiliation: Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Guehl
authors.affiliation: Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; Department of Neurology, University Hospital Bordeaux, France.
authors.forename: François
authors.initials: F
authors.lastname: Tison
authors.affiliation: Motac Neuroscience Ltd, Manchester, UK.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Crossman
authors.affiliation: Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Un Jung
authors.initials: UJ
authors.lastname: Kang
authors.affiliation: Michigan State University, College of Human Medicine, Department of Translational Science and Molecular Medicine & The Udall Center of Excellence in Parkinson's Disease Research, 333 Bostwick Ave NE, Grand Rapids, MI 49503, USA.
authors.forename: Kathy
authors.initials: K
authors.lastname: Steece-Collier
authors.affiliation: Morton & Gloria Shulman Movement Disorders Center, Toronto Western Hospital, Toronto, Ontario M4T 2S8, Canada.
authors.forename: Susan
authors.initials: S
authors.lastname: Fox
authors.affiliation: Department of Biomedical Sciences, Physiology Section, Cagliari University, Cagliari, Italy.
authors.forename: Manolo
authors.initials: M
authors.lastname: Carta
authors.affiliation: Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Angela Cenci
authors.affiliation: Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; Motac Neuroscience Ltd, Manchester, UK. Electronic address: erwan.bezard@u-bordeaux.fr.
authors.forename: Erwan
authors.initials: E
authors.lastname: Bézard
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects*; D002490:Central Nervous System / Q000187:drug effects / Q000503:physiopathology*; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D006801:Humans; D007980:Levodopa / Q000009:adverse effects*; D010300:Parkinson Disease / Q000188:drug therapy
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa
keywords: Animal models; D1 receptor; Dopamine; Dyskinesia; L-dopa; Parkinson's disease