%0 Journal Article
%T NMDA receptor regulation of levodopa-induced behavior and changes in striatal G protein-coupled receptor kinase 6 and  -arrestin-1 expression in parkinsonian rats
%A Wu N
%A Song L
%A Yang X
%A Yuan W
%J Clinical Interventions in Aging
%D 2013
%I Dove Medical Press
%X Na Wu, Lu Song, Xinxin Yang, Weien Yuan, Zhenguo Liu Department of Neurology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People¡¯s Republic of China Background: Parkinson¡¯s disease is a neurodegenerative disorder caused by loss of dopaminergic neurons in the substantia nigra. The dopamine precursor, levodopa, remains the most effective and common treatment for this disorder. However, long-term administration of levodopa is known to induce characteristic dyskinesia, and molecular mechanisms underlying dyskinesia are poorly understood. Methods: In this study, we investigated the effect of 6-hydroxydopamine lesions in dopaminergic neurons and chronic treatment with levodopa on expression of G protein-coupled receptor kinase 6 and  -arrestin-1, two key regulators of G protein-coupled receptors, in the rat striatum. Results: We found that a unilateral 6-hydroxydopamine lesion reduced expression of G protein-coupled receptor kinase 6 and  -arrestin-1 protein in the lesioned striatum. Reduction of these two proteins persisted in 6-hydroxydopamine-lesioned rats on chronic levodopa treatment for 23 days. In addition, coadministration of the N-methyl-D-aspartate receptor antagonist, MK-801, and levodopa reversed the reduction of G protein-coupled receptor kinase 6 and  -arrestin-1 in the striatum. MK-801 also attenuated levodopa-induced dyskinetic behavior. Conclusion: These data indicate that G protein-coupled receptor kinase 6 and  -arrestin-1 in striatal neurons are sensitive to dopamine depletion and are downregulated in rats with Parkinson¡¯s disease and in levodopa-treated rats with the disease. This downregulation seems to require activation of N-methyl-D-aspartate glutamate receptors. Keywords: dopamine, levodopa, levodopa-induced dyskinesias, G protein-coupled receptors, G protein-coupled receptor kinase dyskinesia
%U http://www.dovepress.com/nmda-receptor-regulation-of-levodopa-induced-behavior-and-changes-in-s-a12572