Effects of 6-methoxy-1,2,3,4-tetrahydro-beta-carboline (6-MeO-THbetaC) on audiogenic seizures in DBA/2J mice.

It was found previously that 6-methoxy-1,2,3,4-tetrahydro-beta-carboline (6-MeO-THbetaC) increased brain concentration of the neurotransmitter serotonin (5-HT) and decreased the concentration of its metabolite 5-hydroxyindole acetic acid (5-HIAA) at the same time the compound attenuated audiogenic seizures (AGS) in DBA/2J mice. In the present study we determined the time-course and dose-response effects of 6-MeO-THbetaC for blockade of AGS. Drugs sharing common effects with 6-MeO-THbetaC were also tested. At a dose of 100 mg/kg, 6-MeO-THbetaC blocked AGS between 10 min and 12 hr after injection, with maximal inhibition at 1 hr at which time a dose-related decrease in AGS was also demonstrated. All of the drugs tested which blocked AGS, including 6-MeO-THbetaC, THbetaC, 5-Hydroxytryptophan, chlorimipramine and pargyline, have biochemical similarities suggesting that facilitating serotonin function may be responsible for seizure-attenuating effects.