METHIONINE SULFOXIMINE INCREASES ACETYLCHOLINE LEVEL IN THE RAT-BRAIN - NO RELATION WITH EPILEPTOGENESIS

METHIONINE sulfoximine induces epileptiform convulsions in rats. A possible involvement of acetylcholine in the onset of convulsions was investigated. A subconvulsive dose of methionine sulfoximine increased the brain acetylcholine concentration. After administration of a convulsive dose, atropine neither prevented the onset of the seizures nor prevented the increase in acetylcholine concentration. Physostigmine enhanced the increase in acetylcholine level but did not modify the time course nor the intensity of the convulsions. L-DOPA suppressed the seizures without inhibiting the increase in acetylcholine level. The choline content decreased after the convulsant dose. The increase in acetylcholine content is therefore not the unique cause of the seizures, which could result from the reduction of striatal inhibition due to a decrease in dopamine level induced by methionine sulfoximine.