The possible role of endogenous glutathione as an anticonvulsant in mice

We have recently found that intracerebroventricular (i.c.v.) administration of glutathione (GSH) inhibits pentylenetetrazol-induced convulsions in mice, suggesting that GSH has an anticonvulsive action. In the present study, we investigated whether endogenous GSH play a role in regulating seizure susceptibility, using L-buthionine-[S,R]-sulfoximine (BSO), a specific inhibitor of GSH biosynthesis. BSO treatment (3.2 micromol i.c.v. x 2, 48 and 24 h prior to experiments) decreased brain GSH level to 31.5% of control, and potentiated pentylenetetrazol-induced convulsions. Potentiation of convulsions by BSO treatment was recovered by supplying GSH (10 nmol, i.c.v.). These results suggest that endogenous GSH functions as an anticonvulsant.