The metabolism of 5-hydroxytryptamine in the methionine sulfoximine epileptogenic rat brain
Sellinger, O.Z.; Dietz, D.D.
Journal of Pharmacology and Experimental Therapeutics 216(1): 77-82
1981
ISSN/ISBN: 0022-3565 PMID: 6161244 Document Number: 180529
An investigation of the effects of the slow-acting convulsant agent L-methionine-dl-sulfoximine (MSO) one regional metabolism of cerebral 5-hydroxytryptamine (5-HT) revealed the of MSO following: 5-HT levels decreased in the brainstem, the midbrain, the hippocampus and the cortex, and those of 5-hydroxyindoleacetic in the cortex and the midbrain 5 h after a single dose (150 mg/kg i.p.) of MSO; pretreatment with MSO + p-chlorophenylalanine caused a greater reduction of 5-HT levels in the midbrain and the hypothalamus than was noted after p-chlorophenylalanine alone; pretreatment with MSO antagonized the elevation of 5-HT levels noted in the brainstem and the cortex 30 min after the administration of clorgyline, an inhibitor of monoamine oxidase, type A; pretreatment with MSO antagonized the reduction of 5-hydroxyindoleacetic acid levels noted in the cortex and in the striatum 30 min and in the striatum 120 min, after the administration of clorgyline; and pretreatment with MSO also led to a significant reduction of the formation of [14C]5-HT from intra-arterially administered [14C]5-hydroxytryptophan initially in the brainstem and subsequently in the striatum. The effect of MSO on the action of p-chlorphenylalanine, noted over a 12 h experimental period, suggests an increased rate of 5-HT turnover in the midbrain and the hypothalamus; its effect on the action of clorgyline, noted over a 5 h experimental period, suggests a decreased rate of 5-HT turnover in the cortex, the brainstem and the striatum. The findings obtained using MSO and [14C]5-hydroxytryptophan suggest a slowdown of the turnover of 5-HT, as measured over 10-40 min, in the brainstem, the midbrain and the striatum, but not in the cortex. MSO-elicited, time-dependent, regional perturbations of 5-HT metabolism apparently mediate the desynchronization of the firing rates of inhibitory serotonergic fibers, and thus help to create the MSO epileptogenic state.