Academic Journal
Co-administration of cannabidiol and capsazepine reduces L-DOPA-induced dyskinesia in mice: Possible mechanism of action
| العنوان: | Co-administration of cannabidiol and capsazepine reduces L-DOPA-induced dyskinesia in mice: Possible mechanism of action |
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| المؤلفون: | Maurício dos-Santos-Pereira, Célia Aparecida da-Silva, Francisco Silveira Guimarães, Elaine Del-Bel |
| المصدر: | Neurobiology of Disease, Vol 94, Iss , Pp 179-195 (2016) |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2016 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Cannabinoid, LID, AIMs, Neuroinflammation, Anandamide, CB1, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571 |
| الوصف: | Pharmacological manipulation of the endocannabinoid system represents a promising therapy to alleviate L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID) in Parkinson's disease (PD). Our aim was to verify whether cannabidiol (CBD), the major non-psychoactive constituent of Cannabis sativa, modifies LID. To this end, the present study employed the 6-hydroxydopamine-neurotoxin model in male C57⁄BL6 mice to reproduce the pattern of cell death present in PD patients. Unilateral striatal lesioned mice received L-DOPA for 21 days, developing severe axial, limb, locomotor and orofacial abnormal involuntary movements (AIMs). Following that, the animals were treated with CBD (intraperitoneally) before L-DOPA for three days, alone or in combination with antagonists of the Transient Receptor Potential Vanniloid-1 (TRPV-1), cannabinoid type 1 (CB1) or Peroxisome Proliferator-Activated type gamma (PPARγ) receptors. Nor CBD or any of the antagonists individually were effective in decreasing AIMs. CBD administered with the TRPV-1 antagonist capsazepine (CPZ) reduced AIMs. Treatment with arachidonoyl-serotonin (AA-5-HT), an inhibitor of the enzyme responsible for anandamide metabolism fatty acid amide hydrolase (FAAH) and a TRPV-1 blocker, reproduced these findings. The CB1 receptor antagonist AM251 or the PPARγ receptor antagonist GW9662 selectively reversed the antidyskinetic effect of CPZ + CBD, with AM251 decreasing limb and orofacial AIMs and GW9662 reducing axial AIMs. The decrease of LID by CPZ + CBD was associated with a reduction in the molecular markers phospho-acetylated histone H3 and phosphorylated extracellular signal-regulated protein kinases 1 and 2. L-DOPA treatment in hemiparkinsonian mice increased the pro-inflammatory markers cyclooxygenase-2 and nuclear factor-kappa B in the lesioned striatum. These markers were also decreased by CPZ + CBD treatment. Our study indicates that CBD, together with a TRPV-1 antagonist, reduces LID by acting on CB1 and PPARγ receptors and reducing the expression of ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1095-953X |
| Relation: | http://www.sciencedirect.com/science/article/pii/S096999611630153X; https://doaj.org/toc/1095-953X; https://doaj.org/article/0ec2d7c6b992480981aa4b87f6aeee2a |
| DOI: | 10.1016/j.nbd.2016.06.013 |
| الاتاحة: | https://doi.org/10.1016/j.nbd.2016.06.013 https://doaj.org/article/0ec2d7c6b992480981aa4b87f6aeee2a |
| رقم الانضمام: | edsbas.B54DEF2A |
| قاعدة البيانات: | BASE |
| تدمد: | 1095953X |
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| DOI: | 10.1016/j.nbd.2016.06.013 |