title: Riluzole reduces incidence of abnormal movements but not striatal cell death in a primate model of progressive striatal degeneration.
abstract: Riluzole has been shown recently to increase life expectancy in patients with amyotrophic lateral sclerosis. A number of experimental studies also suggest that this compound may be a neuroprotectant. We have investigated in baboons whether riluzole would protect striatal neurons from a prolonged 3-nitropropionic acid (3NP) treatment and ameliorate the associated motor symptoms. In animals receiving 3NP and the solvent of riluzole, 12 weeks of high-dose 3NP treatment resulted in the appearance of persistent leg dystonia and significant increases in the incidence of three categories of abnormal movements and in the dyskinesia index in the apomorphine test (0.5 mg/kg i.m.). Quantitative assessment of these behavioral deficits using a video movement analysis system demonstrated a significant decrease in locomotor activity and peak tangential velocity in 3NP-treated animals compared to controls. Histological analysis showed the presence of severe, bilateral, striatal lesions, localized in both caudate and putamen. Cotreatment with riluzole (4 mg/kg i.p., twice daily) significantly reduced the dyskinesia index (-35%, P < 0.02) in the apomorphine test. In the quantitative behavioral analysis, riluzole significantly ameliorated the decrease in peak tangential velocity (P < 0.02) but not the decrease in locomotor activity observed after 3NP. Comparative histological analysis of the two groups of treated animals did not demonstrate a clear neuroprotective effect of riluzole. The present study suggests that one potential therapeutic interest for riluzole in neurodegenerative disorders may reside in the reduction of motor symptoms associated with striatal lesions.
authors.affiliation: URA CEA/CNRS 2210 DRM, DSV, Service Hospitalier Frédéric Joliot, Orsay, France.
authors.forename: S
authors.initials: S
authors.lastname: Palfi
authors.forename: D
authors.initials: D
authors.lastname: Riche
authors.forename: E
authors.initials: E
authors.lastname: Brouillet
authors.forename: M C
authors.initials: MC
authors.lastname: Guyot
authors.forename: V
authors.initials: V
authors.lastname: Mary
authors.forename: F
authors.initials: F
authors.lastname: Wahl
authors.forename: M
authors.initials: M
authors.lastname: Peschanski
authors.forename: J M
authors.initials: JM
authors.lastname: Stutzmann
authors.forename: P
authors.initials: P
authors.lastname: Hantraye
mesh_terms: D000110:Acetylcholinesterase / Q000032:analysis; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D002421:Caudate Nucleus / Q000187:drug effects / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D009069:Movement Disorders / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009410:Nerve Degeneration / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins; D009574:Nitro Compounds; D010215:Papio; D010302:Parkinson Disease, Secondary / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D011422:Propionates; D011699:Putamen / Q000187:drug effects / Q000473:pathology; D019782:Riluzole; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D000978:Antiparkinson Agents; D018696:Neuroprotective Agents; D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; D013844:Thiazoles; D019782:Riluzole; D000110:Acetylcholinesterase; D001058:Apomorphine; C015392:3-nitropropionic acid