Riluzole protects from motor deficits and striatal degeneration produced by systemic 3-nitropropionic acid intoxication in rats.
The putative neuroprotective effect of riluzole was investigated in a rat model of progressive striatal neurodegeneration induced by prolonged treatment (three weeks, intraperitoneal) with 3-nitropropionic acid, an irreversible inhibitor of succinate dehydrogenase. Quantitative analysis of motor behaviour indicated a significant protective effect (60%) of riluzole (8 mg/kg/day) on 3-nitropropionic acid-induced motor deficits as assessed using two independent motor tests. Furthermore, quantitative analysis of 3-nitropropionic acid-induced lesions indicated a significant 84% decrease in the volume of striatal damage produced by 3-nitropropionic acid, the neuroprotective effect apparently being more pronounced in the posterior striatum and pallidum. In addition, it was checked that this neuroprotective effect of riluzole against systemic 3-nitropropionic acid did not result from a decreased bioavailability of the neurotoxin or a direct action of riluzole on 3-nitropropionic acid-induced inhibition of succinate dehydrogenase. We found that riluzole significantly decreased by 48% the size of striatal lesions produced by stereotaxic intrastriatal injection of malonate, a reversible succinate dehydrogenase inhibitor. Furthermore, the inhibition of cortical and striatal succinate dehydrogenase activity induced by systemic 3-nitropropionic acid was left unchanged by riluzole administration. The present results, consistent with a beneficial effect of riluzole in amyotrophic lateral sclerosis, suggest that this compound may be useful in the treatment of chronic neurodegenerative diseases.
Guyot
M C
MC
Service Hospitalier Frédéric Joliot, Unité de Recherche Associée 2210 Commissariat à l'Energie Atomique-Centre National de la Recherche Scientifique, Département de Recherche Médicale, Orsay, France.
Palfi
S
S
Stutzmann
J M
JM
Mazière
M
M
Hantraye
P
P
Brouillet
E
E
D000818:Animals; D000959:Antihypertensive Agents / Q000633:toxicity*; D003342:Corpus Striatum / Q000473:pathology / Q000503:physiopathology*; D007274:Injections, Intraperitoneal; D008297:Male; D008314:Malonates / Q000633:toxicity; D008845:Microinjections; D009069:Movement Disorders / Q000188:drug therapy* / Q000401:mortality; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity; D009574:Nitro Compounds; D011422:Propionates / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019782:Riluzole / Q000494:pharmacology*; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors; D016019:Survival Analysis
D000959:Antihypertensive Agents; D008314:Malonates; D018696:Neuroprotective Agents; D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; D019782:Riluzole; C030290:malonic acid; D013385:Succinate Dehydrogenase; C015392:3-nitropropionic acid