Increased D1 dopamine receptor signaling in levodopa-induced dyskinesia.
Ann Neurol.. 2004-10-27; 57(1): 17-26
DOI: 10.1002/ana.20296
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1. Ann Neurol. 2005 Jan;57(1):17-26.
Increased D1 dopamine receptor signaling in levodopa-induced dyskinesia.
Aubert I(1), Guigoni C, Håkansson K, Li Q, Dovero S, Barthe N, Bioulac BH, Gross
CE, Fisone G, Bloch B, Bezard E.
Author information:
(1)Centre National de la Recherche Scientifique Unite Mixte de Recherche 5541,
Bordeaux Cedex, France.
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.
DOI: 10.1002/ana.20296
PMID: 15514976 [Indexed for MEDLINE]