Effects of Fenfluramine and 5-methoxy-N, N-dimethyltryptamine on serotonergic neuron in 2-month-and 10-month-old mice

The involvement of presynaptic serotonergic activity in the fenfluramine-induced head twitches was investigated using various drugs in 2-month-and 10-month-old mice. Mice administerd fenfluramine produced head twitches which were inhibited by methysergide and cyproheptadine, serotonergic antagonist. The freqency of head twitches induced by fenfluramine and 5-methoxy-N, N-dimethyltryptamine (5-MeODMT) was higher in 10-month-old mice than in 2-month-old mice. Pretreatments with p-chlorophnylalanine (PCPA), a tyrosine hydroxylase inhibitor, and reserpine an amine depletor, significantly potentiated 5-MeODMT-induced head twitches in 2-month-old mice, but did not affect those in 10-month-old mice. Pretreatment with PCPA inhibited fenfluramine : induced head twitches in either 2-month-or 10-monthe-old mice, whereas pretreatment with reserpine inhibited the head twitches in 10-month-old mice but did not change the head twitches in 2-month-old mice. These results suggest that fenfluramine-induced head twitches may be mediated by endogenous serotonin which is released from presynapse of central serotonergic neuron. The decreased function of presynaptic receptormay potentiate the postsynaptic receptor activities, and contribute to the increase head twitches induced by fenfluramine and 5-MeODMT, with increasing age in the mouse.