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.