Behaviour of ?-methylserotonin in rat brain synaptosomes

Twenty-four h after administration of ?-methyl-dl-tryptophan (AMTP) to rats intrasynaptosomal ?-methylserotonin (AM5HT) levels were 5.5-fold greater than those of serotonin (5HT) in control animals, and were accompanied by a 90% reduction in 5HT concentrations. Behaviour of AM5HT in nerve terminals was examined by use of synaptosomes prepared from brains of rats given AMTP. The relative depletion of intrasynaptosomal AM5HT and 5HT levels induced by K(+) was equivalent over the range of 5-100 mM KCl. The concentration of intrasynaptosomal AM5HT was significantly reduced in rats treated with reserpine following AMTP injection. Similarly, rats treated with a neurotoxic regimen of p-chloroamphetamine prior to AMTP administration also showed marked reduction in synaptosomal AM5HT levels. Synaptosomes prepared from brains of untreated rats accumulated AM5HT in a temperature-dependent fashion that was inhibited by co-incubation with 5HT or fluoxetine. These results support the hypotheses that AM5HT is stored in synaptosomes derived from serotonergic neurons and that AM5HT is accumulated into and released from brain synaptosomes in a manner similar to 5HT.