METHIONINE SULFOXIMINE HAS NO MAJOR EFFECT ON GAMMA-AMINOBUTYRIC-ACIDCONCENTRATION IN THE RAT-BRAIN

In previous investigations, we have shown that the convulsant methioni ne sulfoximine selectively diminished the concentrations of certain ca techolamines and indoleamines and increased the concentration of acety lcholine in the rat encephalon. These changes were not related to the convulsion genesis. In order to look for another neurotransmitter syst em which could be involved in epileptogenesis induced by methionine su lfoximine, the effects of this drug on the GABA level were studied in the present work. The GABA concentration was measured using high perfo rmance liquid chromatography with electrochemical detection. When meth ionine sulfoximine (100 mg/kg body weight) was intraperitoneally injec ted to rats, GABA concentration did not significantly change during th e convulsive period, neither during the preconvulsive nor the postconv ulsive periods except in the hippocampus where a decrease was recorded during the convulsive period. Examination of the periconvulsive perio d did not reveal any important transient changes in GABA concentration . When the convulsant doses were increased to 150 mg/kg and to 200 mg/ kg, the results were almost the same as the preceding results. Through out the experiments, the values recorded in treated animals were sligh tly smaller than those recorded in saline controls but, the difference s were not significant at the conventional Student's t test level (p<0 .05), except in the hippocampus. The administration of 80 mg/kg induce d convulsions in many animals, but the GABA concentration did not chan ge in any region. These results show that, irrespective of the brain a rea and of the dose used, methionine sulfoximine does not induce impor tant changements in GABA concentration.