title: The combination of oral L-DOPA/rimonabant for effective dyskinesia treatment and cytological preservation in a rat model of Parkinson's disease and L-DOPA-induced dyskinesia.
abstract: Parkinson's disease is the second most prevalent neurodegenerative disease in the world. Its treatment is limited so far to the management of parkinsonian symptoms with L-DOPA (LD). The long-term use of LD is limited by the development of L-DOPA-induced dyskinesias and dystonia. However, recent studies have suggested that pharmacological targeting of the endocannabinoid system may potentially provide a valuable therapeutic tool to suppress these motor alterations. In the present study, we have explored the behavioral (L-DOPA-induced dyskinesias severity) and cytological (substantia nigra compacta neurons and striatum neuropil preservation) effects of the oral coadministration of LD and rimonabant, a selective antagonist of CB1 receptors, in the 6-hydroxydopamine rat model of Parkinson's disease. Oral coadministration of LD (30 mg/kg) and rimonabant (1 mg/kg) significantly decreased abnormal involuntary movements and dystonia, possibly through the conservation of some functional tyrosine hydroxylase-immunoreactive dopaminergic cells, which in turn translates into a well-preserved neuropil of a less denervated striatum. Our results provide anatomical evidence that long-term coadministration of LD with cannabinoid antagonist-based therapy may not only alleviate specific motor symptoms but also delay/arrest the degeneration of striatal and substantia nigra compacta cells.
authors.affiliation: Neuromorphology Laboratory, Neuroscience Department, FES Iztacala, National University of Mexico (UNAM), Tlalnepantla, Mexico.
authors.forename: Ana L
authors.initials: AL
authors.lastname: Gutiérrez-Valdez
authors.forename: Ricardo
authors.initials: R
authors.lastname: García-Ruiz
authors.forename: Verónica
authors.initials: V
authors.lastname: Anaya-Martínez
authors.forename: Carmen
authors.initials: C
authors.lastname: Torres-Esquivel
authors.forename: Jesús
authors.initials: J
authors.lastname: Espinosa-Villanueva
authors.forename: Leonardo
authors.initials: L
authors.lastname: Reynoso-Erazo
authors.forename: Rocio
authors.initials: R
authors.lastname: Tron-Alvarez
authors.forename: Patricia
authors.initials: P
authors.lastname: Aley-Medina
authors.forename: Javier
authors.initials: J
authors.lastname: Sánchez-Betancourt
authors.forename: Enrique
authors.initials: E
authors.lastname: Montiel-Flores
authors.forename: María R
authors.initials: MR
authors.lastname: Avila-Costa
mesh_terms: D000284:Administration, Oral; D000818:Animals; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D004295:Dihydroxyphenylalanine / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy*; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy / Q000473:pathology*; D019581:Neuropil / Q000166:cytology; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D000077285:Rimonabant; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D063387:Cannabinoid Receptor Antagonists; D015259:Dopamine Agents; D010880:Piperidines; D011720:Pyrazoles; D004295:Dihydroxyphenylalanine; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D000077285:Rimonabant