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The CB1 cannabinoid receptor agonist reduces L-DOPA-induced motor fluctuation and ERK1/2 phosphorylation in 6-OHDA-lesioned rats

The dopamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) has been used as an effective drug for treating dopamine depletion-induced Parkinson’s disease (PD). However, long-term administration of L-DOPA produces motor complications. L-DOPA has also been found to modify the two key signaling casca...

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Autores principales: Song, Lu, Yang, Xinxin, Ma, Yaping, Wu, Na, Liu, Zhenguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226453/
https://www.ncbi.nlm.nih.gov/pubmed/25395834
http://dx.doi.org/10.2147/DDDT.S60944
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author Song, Lu
Yang, Xinxin
Ma, Yaping
Wu, Na
Liu, Zhenguo
author_facet Song, Lu
Yang, Xinxin
Ma, Yaping
Wu, Na
Liu, Zhenguo
author_sort Song, Lu
collection PubMed
description The dopamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) has been used as an effective drug for treating dopamine depletion-induced Parkinson’s disease (PD). However, long-term administration of L-DOPA produces motor complications. L-DOPA has also been found to modify the two key signaling cascades, protein kinase A/dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) and extracellular signal-regulated kinases 1 and 2 (ERK1/2), in striatal neurons, which are thought to play a pivotal role in forming motor complications. In the present study, we tested the possible effect of a CB1 cannabinoid receptor agonist on L-DOPA-stimulated abnormal behavioral and signaling responses in vivo. Intermittent L-DOPA administration for 3 weeks induced motor fluctuation in a rat model of PD induced by intrastriatal infusion of dopamine-depleting neurotoxin 6-hydroxydopamine (6-OHDA). A single injection of a CB1 cannabinoid receptor agonist WIN-55,212-2 had no effect on L-DOPA-induced motor fluctuation. However, chronic injections of WIN-55,212-2 significantly attenuated abnormal behavioral responses to L-DOPA in 6-OHDA-lesioned rats. Similarly, chronic injections of WIN-55,212-2 influence the L-DOPA-induced alteration of DARPP-32 and ERK1/2 phosphorylation status in striatal neurons. These data provide evidence for the active involvement of CB1 cannabinoid receptors in the regulation of L-DOPA action during PD therapy.
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spelling pubmed-42264532014-11-13 The CB1 cannabinoid receptor agonist reduces L-DOPA-induced motor fluctuation and ERK1/2 phosphorylation in 6-OHDA-lesioned rats Song, Lu Yang, Xinxin Ma, Yaping Wu, Na Liu, Zhenguo Drug Des Devel Ther Original Research The dopamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) has been used as an effective drug for treating dopamine depletion-induced Parkinson’s disease (PD). However, long-term administration of L-DOPA produces motor complications. L-DOPA has also been found to modify the two key signaling cascades, protein kinase A/dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) and extracellular signal-regulated kinases 1 and 2 (ERK1/2), in striatal neurons, which are thought to play a pivotal role in forming motor complications. In the present study, we tested the possible effect of a CB1 cannabinoid receptor agonist on L-DOPA-stimulated abnormal behavioral and signaling responses in vivo. Intermittent L-DOPA administration for 3 weeks induced motor fluctuation in a rat model of PD induced by intrastriatal infusion of dopamine-depleting neurotoxin 6-hydroxydopamine (6-OHDA). A single injection of a CB1 cannabinoid receptor agonist WIN-55,212-2 had no effect on L-DOPA-induced motor fluctuation. However, chronic injections of WIN-55,212-2 significantly attenuated abnormal behavioral responses to L-DOPA in 6-OHDA-lesioned rats. Similarly, chronic injections of WIN-55,212-2 influence the L-DOPA-induced alteration of DARPP-32 and ERK1/2 phosphorylation status in striatal neurons. These data provide evidence for the active involvement of CB1 cannabinoid receptors in the regulation of L-DOPA action during PD therapy. Dove Medical Press 2014-11-04 /pmc/articles/PMC4226453/ /pubmed/25395834 http://dx.doi.org/10.2147/DDDT.S60944 Text en © 2014 Song et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Song, Lu
Yang, Xinxin
Ma, Yaping
Wu, Na
Liu, Zhenguo
The CB1 cannabinoid receptor agonist reduces L-DOPA-induced motor fluctuation and ERK1/2 phosphorylation in 6-OHDA-lesioned rats
title The CB1 cannabinoid receptor agonist reduces L-DOPA-induced motor fluctuation and ERK1/2 phosphorylation in 6-OHDA-lesioned rats
title_full The CB1 cannabinoid receptor agonist reduces L-DOPA-induced motor fluctuation and ERK1/2 phosphorylation in 6-OHDA-lesioned rats
title_fullStr The CB1 cannabinoid receptor agonist reduces L-DOPA-induced motor fluctuation and ERK1/2 phosphorylation in 6-OHDA-lesioned rats
title_full_unstemmed The CB1 cannabinoid receptor agonist reduces L-DOPA-induced motor fluctuation and ERK1/2 phosphorylation in 6-OHDA-lesioned rats
title_short The CB1 cannabinoid receptor agonist reduces L-DOPA-induced motor fluctuation and ERK1/2 phosphorylation in 6-OHDA-lesioned rats
title_sort cb1 cannabinoid receptor agonist reduces l-dopa-induced motor fluctuation and erk1/2 phosphorylation in 6-ohda-lesioned rats
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226453/
https://www.ncbi.nlm.nih.gov/pubmed/25395834
http://dx.doi.org/10.2147/DDDT.S60944
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