Nature Medicine
9, 762 - 767 (2003)
Published online: 12 May 2003; | doi:10.1038/nm875
Attenuation of levodopa-induced dyskinesia by normalizing dopamine D3 receptor functionErwan Bézard1, Sandrine Ferry2, Ulrich Mach3, Holger Stark3, Ludovic Leriche2, Thomas Boraud1, Christian Gross1
& Pierre Sokoloff21
Basal Gang, Laboratoire de Neurophysiologie, CNRS UMR 5543, Université Victor Segalen, 33076 Bordeaux, France. 2
Unité de Neurobiologie et Pharmacologie Moléculaire, INSERM U 573, 75014 Paris, France. 3
Biozentrum, Johann Wolfgang Goethe-Universität, 60439 Frankfurt am Main, Germany.
Correspondence should be addressed to Erwan Bézard erwan.bezard@umr5543.u-bordeaux2.fr or Pierre Sokoloff sokol@broca.inserm.frIn monkeys rendered parkinsonian with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), expression of the dopamine D3 receptor was decreased. However, levodopa-induced dyskinesia (LID), similar to the debilitating and pharmacoresistant involuntary movements elicited after long-term treatment with levodopa in patients with Parkinson disease (PD), was associated with overexpression of this receptor. Administration of a D3 receptor−selective partial agonist strongly attenuated levodopa-induced dyskinesia, but left unaffected the therapeutic effect of levodopa. In contrast, attenuation of dyskinesia by D3 receptor antagonists was accompanied by the reappearance of PD-like symptoms. These results indicated that the D3 receptor participated in both dyskinesia and the therapeutic action of levodopa, and that partial agonists may normalize D3 receptor function and correct side effects of levodopa therapy in patients with PD.
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