IFIBIO HOUSSAY   25014
INSTITUTO DE FISIOLOGIA Y BIOFISICA BERNARDO HOUSSAY
Unidad Ejecutora - UE
artículos
Título:
Beneficial effects of the phytocannabinoid Δ9-THCV in L-DOPA-induced dyskinesia in Parkinson's disease
Autor/es:
ESPADAS, ISABEL; BURGAZ, SONIA; MORATALLA, ROSARIO; KEIFMAN, ETTEL; GARCÍA, CONCEPCIÓN; PALOMO-GARO, CRISTINA; FERNÁNDEZ-RUIZ, JAVIER
Revista:
NEUROBIOLOGY OF DISEASE
Editorial:
ACADEMIC PRESS INC ELSEVIER SCIENCE
Referencias:
Año: 2020 vol. 141
ISSN:
0969-9961
Resumen:
The antioxidant and CB2 receptor agonist properties of Δ9-tetrahydrocannabivarin (Δ9-THCV) afforded neuroprotectionin experimental Parkinson´s disease (PD), whereas its CB1 receptor antagonist profile at doses lowerthan 5 mg/kg caused anti-hypokinetic effects. In the present study, we investigated the anti-dyskinetic potentialof Δ9-THCV (administered i.p. at 2 mg/kg for two weeks), which had not been investigated before. This objectivewas investigated after inducing dyskinesia by repeated administration of L-DOPA (i.p. at 10 mg/kg) in a geneticmodel of dopaminergic deficiency, Pitx3ak mutant mice, which serves as a useful model for testing anti-dyskineticagents. The daily treatment of these mice with L-DOPA for two weeks progressively increased the timespent in abnormal involuntary movements (AIMs) and elevated their horizontal and vertical activities (asmeasured in a computer-aided actimeter), signs that reflected the dyskinetic state of these mice. Interestingly,when combined with L-DOPA from the first injection, Δ9-THCV delayed the appearance of all these signs anddecreased their intensity, with a reduction in the levels of FosB protein and the histone pAcH3 (measured byimmunohistochemistry), which had previously been found to be elevated in the basal ganglia in L-DOPA-induceddyskinesia. In addition to the anti-dyskinetic effects of Δ9-THCV when administered at the onset of L-DOPAtreatment, Δ9-THCV was also effective in attenuating the intensity of dyskinesia when administered for threeconsecutive days once these signs were already present (two weeks after the onset of L-DOPA treatment). Insummary, our data support the anti-dyskinetic potential of Δ9-THCV, both to delay the occurrence and to attenuatethe magnitude of dyskinetic signs. Although further studies are clearly required to determine the clinicalsignificance of these data in humans, the results nevertheless situate Δ9-THCV in a promising position for developinga cannabinoid-based therapy for patients with PD.