Involvement of NO in the convulsive behavior and oxidative damage induced by the intrastriatal injection of methylmalonate

Acute intrastriatal administration of methylmalonic acid (MMA) induces convulsions through NMDA receptor-mediated mechanisms and increases production of end products of oxidative damage. Although it has been demonstrated that nitric oxide (NO) production increases with NMDA receptor stimulation and contributes to the oxidative damage observed in several neurodegenerative disorders, the role of NO in MMA-induced convulsions has not been investigated to date. In the present study we investigated the effects of the intrastriatal injection of Nω-nitro-l-arginine methyl ester (l-NAME: 10−4 to 100 nmol/0.5 μl) on the convulsions and striatal protein carbonylation induced by the intrastriatal injection of MMA (4.5 μmol/1.5 μl). l-NAME (10−3 to 10−1 nmol) protected against MMA-induced convulsions and protein carbonylation ex vivo. These results suggest the involvement of NO in the convulsive behavior and protein carbonylation elicited by MMA.