Increased D1 dopamine receptor signaling in levodopa-induced dyskinesia

Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa therapy for Parkinson's disease. Although changes affecting D1 and D2 dopamine receptors have been studied in association with this condition, no causal relationship has yet been established. Taking advantag...

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Veröffentlicht in:	Annals of neurology Jg. 57; H. 1; S. 17 - 26
Hauptverfasser:	Aubert, Incarnation, Guigoni, Céline, Håkansson, Kerstin, Li, Qin, Dovero, Sandra, Barthe, Nicole, Bioulac, Bernard H., Gross, Christian E., Fisone, Gilberto, Bloch, Bertrand, Bezard, Erwan
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.01.2005 Willey-Liss
Schlagworte:	1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - pharmacology 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine - pharmacology Analysis of Variance Animals Antiparkinson Agents - adverse effects Autoradiography - methods Behavior, Animal Biological and medical sciences Blotting, Western - methods Cyclin-Dependent Kinase 5 Cyclin-Dependent Kinases Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Disease Models, Animal Dopamine and cAMP-Regulated Phosphoprotein 32 Dopamine Plasma Membrane Transport Proteins Dose-Response Relationship, Drug Drug Interactions Drug toxicity and drugs side effects treatment Dyskinesia, Drug-Induced - etiology Dyskinesia, Drug-Induced - metabolism Female Guanosine 5'-O-(3-Thiotriphosphate) - pharmacokinetics Immunohistochemistry - methods In Situ Hybridization - methods Isotopes - pharmacokinetics Levodopa - adverse effects Macaca fascicularis Medical sciences Membrane Glycoproteins - metabolism Membrane Transport Proteins - metabolism Motor Activity - drug effects Nerve Tissue Proteins - metabolism Neurology Nortropanes - pharmacokinetics Parkinsonian Disorders - drug therapy Parkinsonian Disorders - metabolism Parkinsonian Disorders - physiopathology Pharmacology. Drug treatments Phosphoproteins - metabolism Radioligand Assay - methods Receptors, Dopamine D1 - agonists Receptors, Dopamine D1 - genetics Receptors, Dopamine D1 - metabolism Receptors, Dopamine D2 - genetics Receptors, Dopamine D2 - metabolism Signal Transduction - drug effects Substantia Nigra - drug effects Substantia Nigra - metabolism Time Factors Toxicity: nervous system and muscle Tyrosine 3-Monooxygenase - metabolism Signal transduction Nervous system diseases Central nervous system disease D1 Dopamine receptor Levodopa Neurological disorder Antiparkinson agent Motor control Cerebral disorder Extrapyramidal syndrome Involuntary movement Dyskinesia
ISSN:	0364-5134, 1531-8249
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Zusammenfassung:	Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa therapy for Parkinson's disease. Although changes affecting D1 and D2 dopamine receptors have been studied in association with this condition, no causal relationship has yet been established. Taking advantage of a monkey brain bank constituted to study levodopa‐induced dyskinesia, we report changes affecting D1 and D2 dopamine receptors within the striatum of normal, parkinsonian, nondyskinetic levodopa‐treated parkinsonian, and dyskinetic levodopa‐treated parkinsonian animals. Whereas D1 receptor expression itself is not related to dyskinesia, D1 sensitivity per D1 receptor measured by D1 agonist‐induced [35S]GTPγS binding is linearly related to dyskinesia. Moreover, the striata of dyskinetic animals show higher levels of cyclin‐dependent kinase 5 (Cdk5) and of the dopamine‐ and cAMP‐regulated phosphoprotein of 32kDa (DARPP‐32). Our data suggest that levodopa‐induced dyskinesia results from increased dopamine D1 receptor–mediated transmission at the level of the direct pathway. Ann Neurol 2004
Bibliographie:	the Fondation pour la Recherche Médicale the Fédération pour la Recherche sur le Cerveau ArticleID:ANA20296 ark:/67375/WNG-PBCVQ624-2 istex:5D90030B94E7F93E57953B603D763F76B206FACF Michael J. Fox Foundation for Parkinson Research ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0364-5134 1531-8249
DOI:	10.1002/ana.20296