Abnormalities of carbohydrate metabolism and monoamine
neurotransmitters have been widely implicated in the pathoetiology of human
epilepsy, and
glucose hypometabolism and/or
tryptophan utilization can be used to localize epileptic foci in the human brain. To investigate the neurochemical changes that underlie seizure susceptibility we studied four strains of mice that respond differently to the
convulsant methionine sulfoximine (MSO).
Seizures in CBA/J strain were induced by MSO at a dosage half that necessary to provoke
seizures in C57BL/6J, BALB/c, or Swiss mice. We report that brain
glycogen content in response to MSO administration was markedly increased in all four strains of mice. Of the monoamine
neurotransmitters studied, the most prominent change was in brain
serotonin (5-hydroxytryptamine, 5-HT) levels that showed a significant reduction following MSO administration. MSO also lowered the concentration of the
5-HT precursor
tryptophan. Notably, inhibition of the fall in
5-HT levels by coadministration of
5-hydroxytryptophan delayed the onset of MSO-induced
seizures. These results indicate that increased
glycogen content and decreased brain levels of
5-HT and
tryptophan are hallmarks of MSO action in mice, and suggest that defective serotonergic neurotransmission could trigger
glycogen increase and seizure genesis.