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• W2093249737 startingPage "134" @default.
• W2093249737 abstract "L-3,4-Dihydroxyphenylalanine (L-DOPA) is a common and effective treatment for Parkinson's disease, but dyskinesia continues to be a serious adverse effect with chronic use. Evidence suggests that L-DOPA induces increases in dopamine, which then binds to supersensitive dopamine receptors, resulting in dyskinesia. We have shown previously that L-DOPA directly causes stereotypy in rats, suggesting that chronic L-DOPA-induced dyskinesia is also caused by L-DOPA itself. This raises the possibility that other L-DOPA metabolites have a role in dyskinesia. We examined the behavioral effects of five L-DOPA metabolites (3-methoxytyramine, 3-MT; 3,4-dihydroxyphenylalanine, DOPAC; dopamine; homovanillic acid, and 3-o-methyl-DOPA) in rats. A unilateral, intracerebroventricular injection of 3-MT (10-200 microg, 40 microl) over 30 min, dose-dependently increased behavioral activity and stereotypy. This effect was suppressed by the dopamine D1/5-receptor antagonist SCH 23390, but not by the dopamine D2/3/4-receptor antagonist sulpiride. Dopamine denervation resulted in behavioral supersensitivity to 3-MT. Neither dopamine nor DOPAC levels increased in the striatum after 3-MT administration, as measured using in vivo voltammetry. The behavioral changes paralleled a rise in 3-MT in the contralateral striatum. DOPAC also caused behavioral changes and stereotypy, but to a smaller degree than 3-MT. Dopamine-denervated rats did not exhibit a supersensitive response to DOPAC, however. Other L-DOPA metabolites did not cause behavioral effects. These data suggest that 3-MT directly induced dopamine-D1/5-receptor-mediated behavioral changes in rats, and that 3-MT may have a role in dyskinesia due to chronic L-DOPA treatment in Parkinson's disease patients." @default.
• W2093249737 created "2016-06-24" @default.
• W2093249737 creator A5034375268 @default.
• W2093249737 creator A5054010220 @default.
• W2093249737 date "2002-03-01" @default.
• W2093249737 modified "2023-09-27" @default.
• W2093249737 title "Behavioral activity and stereotypy in rats induced by l-DOPA metabolites: a possible role in the adverse effects of chronic l-DOPA treatment of Parkinson’s disease" @default.
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• W2093249737 doi "https://doi.org/10.1016/s0006-8993(02)02238-2" @default.
• W2093249737 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11879803" @default.
• W2093249737 hasPublicationYear "2002" @default.
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