Effect of riluzole on quinolinate-induced neuronal damage in rats: comparison with blockers of glutamatergic neurotransmission.
Intrastriatal injection of quinolinate, an N-methyl-D-aspartate (NMDA) agonist, induces a local neuronal lesion, and provides an excitotoxic model of Huntington's disease. In this study, we investigated the effect of different agents acting at various levels of the glutamatergic neurotransmission: (i) dizocilpine (MK801) (0.5 mg/kg ip) significantly reduced the lesion by 74%; (ii) 6-(1-imidazolyl)-7-nitroquinoxaline-2,3(1H,4H)-dione (YM-90K) (3 x 10 and 3 x 20 mg/kg ip) and (iii) lamotrigine (50 mg/kg ip) had no effect; (iv) riluzole (4 and 8 mg/kg per os) significantly reduced the lesion by 35%. The inefficiency of YM-90K suggested that alpha-amino-3-hydroxy-5-methylisoxasole-4-propionate (AMPA) receptors do not participate to the quinolinate-induced excitotoxicity. The mechanism of action of riluzole may be related also to a combination of its different properties. This study indicates that riluzole may be useful for treatment of Huntington's disease.
Mary
V
V
CNS Pharmaceutical Discovery Research, Neurological Diseases Group, Vitry-sur-Seine, France.
Wahl
F
F
Stutzmann
J M
JM
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology*; D000077213:Lamotrigine; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D017378:Quinolinic Acid / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D019782:Riluzole; D009435:Synaptic Transmission / Q000187:drug effects*; D013844:Thiazoles / Q000494:pharmacology*; D014227:Triazines / Q000494:pharmacology
D000927:Anticonvulsants; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D018091:Receptors, AMPA; D013844:Thiazoles; D014227:Triazines; C086162:6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D019782:Riluzole; D017378:Quinolinic Acid; D000077213:Lamotrigine