Title |
The CB1 cannabinoid receptor agonist reduces L-DOPA-induced motor fluctuation and ERK1/2 phosphorylation in 6-OHDA-lesioned rats
|
---|---|
Published in |
Drug Design, Development and Therapy, November 2014
|
DOI | 10.2147/dddt.s60944 |
Pubmed ID | |
Authors |
Lu Song, Xinxin Yang, Yaping Ma, Na Wu, Zhenguo Liu |
Abstract |
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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | 3% |
Unknown | 33 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Master | 8 | 24% |
Student > Bachelor | 7 | 21% |
Other | 3 | 9% |
Researcher | 3 | 9% |
Student > Ph. D. Student | 2 | 6% |
Other | 4 | 12% |
Unknown | 7 | 21% |
Readers by discipline | Count | As % |
---|---|---|
Psychology | 5 | 15% |
Agricultural and Biological Sciences | 5 | 15% |
Neuroscience | 5 | 15% |
Biochemistry, Genetics and Molecular Biology | 3 | 9% |
Chemistry | 2 | 6% |
Other | 5 | 15% |
Unknown | 9 | 26% |