D-FENFLURAMINE, BUT NOT D-NORFENFLURAMINE, USES CALCIUM TO INCREASE EXTRACELLULAR SEROTONIN

Microdialysis in the hippocampus of freely moving rats was used to ass ess extracellular serotonin (5-HT) in response to local infusion of d- fenfluramine and its metabolite d-norfenfluramine with and without loc al calcium depletion. Verapamil (1 mM) in calcium-free Ringer infused via the microdialysis probe increased extracellular 5-HT and prevented the full increase in extracellular 5-HT normally caused by 1 mM d-fen fluramine. The results suggest d-fenfluramine might act in part as a c alcium channel agonist favoring a calcium influx that in turn would tr igger the exocytotic process in 5-HT terminals. d-norfenfluramine, on the other hand, was capable of releasing 5-HT, in vivo, in spite of de pleted Ca levels.