Neuroprotective effects of riluzole on a model of Parkinson's disease in the rat.
The aim of the present study was to analyse whether riluzole, a compound that interacts with the voltage-dependent sodium channel and impairs glutamatergic transmission, would exhibit a neuroprotective activity in a model of Parkinson's disease in the rat. Impaired skilled forelimb use, circling behavior, and altered dopaminergic metabolism of the mesotelencephalic system were evaluated in unilaterally 6-hydroxydopamine-lesioned rats. Riluzole was administered twice 15 min before, and 24 h after, the lesion. Riluzole reduced both the contralateral rotations induced by apomorphine and the ipsilateral ones elicited by amphetamine. Moreover, the decreased dopaminergic metabolism seen after 6-hydroxydopamine injection was attenuated in the riluzole-treated animals, at both the striatal and nigral levels. These biochemical and behavioral results demonstrate the ability of riluzole partially to protect the degeneration of the nigrostriatal dopaminergic neurons induced by the toxin 6-hydroxydopamine. Perhaps, the most striking evidence for the protective effect of riluzole was that this compound improved the skilled paw use, a complex sensorimotor behavior which is not easily ameliorated by palliative therapies such as dopaminergic grafts. These results extend previous data showing that riluzole counteracts the toxicity induced by 1-methyl-4-1,2,3,6-tetrahydropyridine and 1-methyl-4-phenylpyridinium in rodent dopaminergic neurons. The use of riluzole may be considered of potential interest for the neuroprotective therapy of Parkinson's disease.
Rhône-Poulenc Rorer S.A., Centre de Recherches de Vitry-Alfortville, Départment de Biologie, Vitry-sur-Seine, France.
P
P
Barnéoud
M
M
Mazadier
J M
JM
Miquet
S
S
Parmentier
P
P
Dubédat
A
A
Doble
A
A
Boireau
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology; D005260:Female; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D019782:Riluzole; D013239:Stereotyped Behavior / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D013565:Sympatholytics; D013844:Thiazoles / Q000627:therapeutic use*
D000697:Central Nervous System Stimulants; D018491:Dopamine Agonists; D018696:Neuroprotective Agents; D013565:Sympatholytics; D013844:Thiazoles; D019782:Riluzole; D016627:Oxidopamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000661:Amphetamine; D001058:Apomorphine