English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/217310
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Exportar a otros formatos:

Title

Beneficial effects of the phytocannabinoid Δ9-THCV in L-DOPA-induced dyskinesia in Parkinson's disease

AuthorsEspadas, I.; Keifman E; Palomo-Garo, Cristina; Burgaz, S.; García, C.; Fernández-Ruiz, Javier; Moratalla, Rosario
KeywordsParkinson's disease
L-DOPAL-DOPA-induced dyskinesia
Cannabinoids
Δ9-THCV
CB1 receptors
CB2 receptors
Issue Date2020
PublisherAcademic Press
CitationNeurobiology of Disease 141 (2020)
AbstractThe antioxidant and CB receptor agonist properties of Δ-tetrahydrocannabivarin (Δ-THCV) afforded neuroprotection in experimental Parkinson's disease (PD), whereas its CB receptor antagonist profile at doses lower than 5 mg/kg caused anti-hypokinetic effects. In the present study, we investigated the anti-dyskinetic potential of Δ-THCV (administered i.p. at 2 mg/kg for two weeks), which had not been investigated before. This objective was investigated after inducing dyskinesia by repeated administration of L-DOPA (i.p. at 10 mg/kg) in a genetic model of dopaminergic deficiency, Pitx3 mutant mice, which serves as a useful model for testing anti-dyskinetic agents. The daily treatment of these mice with L-DOPA for two weeks progressively increased the time spent in abnormal involuntary movements (AIMs) and elevated their horizontal and vertical activities (as measured in a computer-aided actimeter), signs that reflected the dyskinetic state of these mice. Interestingly, when combined with L-DOPA from the first injection, Δ-THCV delayed the appearance of all these signs and decreased their intensity, with a reduction in the levels of FosB protein and the histone pAcH3 (measured by immunohistochemistry), which had previously been found to be elevated in the basal ganglia in L-DOPA-induced dyskinesia. In addition to the anti-dyskinetic effects of Δ-THCV when administered at the onset of L-DOPA treatment, Δ-THCV was also effective in attenuating the intensity of dyskinesia when administered for three consecutive days once these signs were already present (two weeks after the onset of L-DOPA treatment). In summary, our data support the anti-dyskinetic potential of Δ-THCV, both to delay the occurrence and to attenuate the magnitude of dyskinetic signs. Although further studies are clearly required to determine the clinical significance of these data in humans, the results nevertheless situate Δ-THCV in a promising position for developing a cannabinoid-based therapy for patients with PD.
Publisher version (URL)http://dx.doi.org/10.1016/j.nbd.2020.104892
URIhttp://hdl.handle.net/10261/217310
DOIhttp://dx.doi.org/10.1016/j.nbd.2020.104892
Identifiersdoi: 10.1016/j.nbd.2020.104892
issn: 1095-953X
Appears in Collections:(IC) Artículos
Files in This Item:
File Description SizeFormat 
Beneficial effects of the.pdf1,1 MBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.