DL-FENFLURAMINE INCREASES THE 5-HT SYNTHESIS RATE IN THE TERMINALS WHILE DECREASING IT IN THE CELL-BODIES OF THE RAT-BRAIN

The rate of 5-HT synthesis in discreet rat brain regions was determine d using the alpha-[C-14]methyl-L-tryptophan autoradiographic method. D L-Fenfluramine (10 mg/kg, i.p.), given 20 min before tracer injection, decreased the rate of 5-HT synthesis in the serotonergic cell bodies (-32% in dorsal and -23% in median raphe nuclei) but increased the rat e in almost all the terminal areas investigated when compared to the r ate in the control (saline treated) rats. The most pronounced increase was observed in the cortex (% difference of control between +22% and +49% in auditory and parietal-sensory-motor cortex, respectively), str iatum (+32% in globus pallidus; +17% median part of caudatus-putamen), superior olive (+36%), dorsal hippocampus (+33%) and ventral thalamus (+29%). Our results suggest that axon terminals respond by increasing 5-HT synthesis, after enhanced release of 5-HT from terminals induced by fenfluramine. This increase in 5-HT synthesis in the terminals pro bably occurs as part of the compensatory mechanisms that replenish the loss of neurotransmitter from the terminal releasible pool. At the sa me time our data suggests that the fenfluramine-induced release of 5-H T in the cell bodies inhibits synthesis of the 5-HT through an autorec eptor.