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Picard, M., Guérin, M., Cloix, J.F., Dufour, T. and Hevor, T.K.

Methionine sulfoximine induces a decrease in the tryptophan level of mouse brain

Biog. Amines (2006) 20 (5-6), 185-192

par Frapart - publié le , mis à jour le

Abstract :

Methionine sulfoximine is well known as a powerful convulsant in many animals. However the actual mechanism of its epileptogenic property is not known. The aim of the present work is to look for a possible effect of methionine sulfoximine on the level of tryptophan because indolamine system was involved in some models of epilepsy. For this Swiss mice were given different doses of methionine sulfoximine and tryptophan concentration was measured using HPLC. During the preconvulsive period no significant change was observed in tryptophan concentration when 100mg/kg of methionine sulfoximine was administered to the animals. Conversely, during the convulsive period, a significant decrease in tryptophan concentration was observed in different regions of the brain including cerebral cortex, striatum, thalamus and cerebellum. During this convulsive period, "grand mal" type seizures were observed. When the animals recovered, no difference was observed in tryptophan concentration between controls and mice submitted to methionine sulfoximine during the post-convulsive period. When different doses of the convulsant were administered the decrease in tryptophan level was significant with 50, 150 and 200mg/kg during the convulsive period, as compared to controls. The present investigation clearly shows a large decrease of about 50% in tryptophan level of mouse brain during the convulsions induced by methionine sulfoximine. Since positron emission tomography reveals also a disturbance in tryptophan utilization in epileptic man, it is possible that tryptophan could be involved in seizure genesis.