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Increased D1 dopamine receptor signaling in levodopa-induced dyskinesia.
Ann Neurol. 2005 Jan; 57(1):17-26.AN

Abstract

Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa therapy for Parkinson's disease. Although changes affecting D(1) and D(2) 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 D(1) and D(2) dopamine receptors within the striatum of normal, parkinsonian, nondyskinetic levodopa-treated parkinsonian, and dyskinetic levodopa-treated parkinsonian animals. Whereas D(1) receptor expression itself is not related to dyskinesia, D(1) sensitivity per D(1) receptor measured by D(1) agonist-induced [(35)S]GTPgammaS 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 D(1) receptor-mediated transmission at the level of the direct pathway.

Authors+Show Affiliations

Aubert I
Centre National de la Recherche Scientifique Unite Mixte de Recherche 5541, Bordeaux Cedex, France.
Guigoni C
No affiliation info available
Håkansson K
No affiliation info available
Li Q
No affiliation info available
Dovero S
No affiliation info available
Barthe N
No affiliation info available
Bioulac BH
No affiliation info available
Gross CE
No affiliation info available
Fisone G
No affiliation info available
Bloch B
No affiliation info available
Bezard E
No affiliation info available

MeSH

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepineAnalysis of VarianceAnimalsAntiparkinson AgentsAutoradiographyBehavior, AnimalBlotting, WesternCyclin-Dependent Kinase 5Cyclin-Dependent KinasesDisease Models, AnimalDopamine Plasma Membrane Transport ProteinsDopamine and cAMP-Regulated Phosphoprotein 32Dose-Response Relationship, DrugDrug InteractionsDyskinesia, Drug-InducedFemaleGuanosine 5'-O-(3-Thiotriphosphate)ImmunohistochemistryIn Situ HybridizationIsotopesLevodopaMacaca fascicularisMembrane GlycoproteinsMembrane Transport ProteinsMotor ActivityNerve Tissue ProteinsNortropanesParkinsonian DisordersPhosphoproteinsRadioligand AssayReceptors, Dopamine D1Receptors, Dopamine D2Signal TransductionSubstantia NigraTime FactorsTyrosine 3-Monooxygenase

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15514976

Citation

Aubert, Incarnation, et al. "Increased D1 Dopamine Receptor Signaling in Levodopa-induced Dyskinesia." Annals of Neurology, vol. 57, no. 1, 2005, pp. 17-26.
Aubert I, Guigoni C, Håkansson K, et al. Increased D1 dopamine receptor signaling in levodopa-induced dyskinesia. Ann Neurol. 2005;57(1):17-26.
Aubert, I., Guigoni, C., Håkansson, K., Li, Q., Dovero, S., Barthe, N., Bioulac, B. H., Gross, C. E., Fisone, G., Bloch, B., & Bezard, E. (2005). Increased D1 dopamine receptor signaling in levodopa-induced dyskinesia. Annals of Neurology, 57(1), 17-26.
Aubert I, et al. Increased D1 Dopamine Receptor Signaling in Levodopa-induced Dyskinesia. Ann Neurol. 2005;57(1):17-26. PubMed PMID: 15514976.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased D1 dopamine receptor signaling in levodopa-induced dyskinesia. AU - Aubert,Incarnation, AU - Guigoni,Céline, AU - Håkansson,Kerstin, AU - Li,Qin, AU - Dovero,Sandra, AU - Barthe,Nicole, AU - Bioulac,Bernard H, AU - Gross,Christian E, AU - Fisone,Gilberto, AU - Bloch,Bertrand, AU - Bezard,Erwan, PY - 2004/10/30/pubmed PY - 2005/3/15/medline PY - 2004/10/30/entrez SP - 17 EP - 26 JF - Annals of neurology JO - Ann Neurol VL - 57 IS - 1 N2 - Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa therapy for Parkinson's disease. Although changes affecting D(1) and D(2) 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 D(1) and D(2) dopamine receptors within the striatum of normal, parkinsonian, nondyskinetic levodopa-treated parkinsonian, and dyskinetic levodopa-treated parkinsonian animals. Whereas D(1) receptor expression itself is not related to dyskinesia, D(1) sensitivity per D(1) receptor measured by D(1) agonist-induced [(35)S]GTPgammaS 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 D(1) receptor-mediated transmission at the level of the direct pathway. SN - 0364-5134 UR - https://www.unboundmedicine.com/medline/citation/15514976/Increased_D1_dopamine_receptor_signaling_in_levodopa_induced_dyskinesia_ DB - PRIME DP - Unbound Medicine ER -