Audiogenic seizures in mice: influence of agents affecting brain serotonin

Brain serotonin levels and susceptibility to audiogenic seizures were examined in a strain of inbred audiosusceptible mice and in control mice at intervals from two hours to one week after treatment with several agents known to modify serotonin metabolism. Although p-chlorophenylalanine produced a gradual decrease in brain serotonin there appeared to be no temporal correlation between this effect and the rapid reduction in seizure susceptibility. 5-Hydroxytryptophan and tranylcypromine led to significant increases in serotonin, but only the former caused a proportinal reduction in seizure activity. Reserpine and alpha-propyldopacetamide decreased serotonin levels but only reserpine caused an intensification of seizure activity proportional to serotonin changes. On the basis of our data, effects of 5-hydroxytryptophan and reserpine on seizure susceptibility appear to be linked to observed brain serotonin levels; further studies are needed to elucidate the mode of action of p-chlorophenylalanine.