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 prolong ed treatment (three weeks, intraperitoneal) with 3-nitropropionic acid , an irreversible inhibitor of succinate dehydrogenase. Quantitative a nalysis 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, q uantitative analysis of 3-nitropropionic acid-induced lesions indicate d a significant 84%, decrease in the volume of striatal damage produce d by 3-nitropropionic acid, the neuroprotective effect apparently bein g more pronounced in the posterior striatum and pallidum. In addition, it was checked that this neuroprotective effect of riluzole against s ystemic 3-nitropropionic acid did not result from a decreased bioavail ability of the neurotoxin or a direct action of riluzole on 3-nitropro pionic acid-induced inhibition of succinate dehydrogenase. We found th at riluzole significantly decreased by 48% the size of striatal lesion s produced by stereotaxic intrastriatal injection of malonate, a rever sible succinate dehydrogenase inhibitor. Furthermore, the inhibition o f cortical and striatal succinate dehydrogenase activity induced by sy stemic 3-nitropropionic acid was left unchanged by riluzole administra tion. The present results, consistent with a beneficial effect of rilu zole in amyotrophic lateral sclerosis, suggest that this compound may be useful in the treatment of chronic neurodegenerative diseases. (C) 1997 IBRO. Published by Elsevier Science Ltd.