RELEASE OF SEROTONIN-INDUCED BY 3,4-METHYLENEDIOXYMETHAMPHETAMINE (MDMA) AND OTHER SUBSTITUTED AMPHETAMINES IN CULTURED FETAL RAPHE NEURONS- FURTHER EVIDENCE FOR CALCIUM-INDEPENDENT MECHANISMS OF RELEASE

The substituted amphetamines 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), p-chloroamphetamine (PCA) and fe nfluramine (FEN) all exert their effects by releasing serotonin (5-HT) from presynaptic nerve terminals. In the current study, we examined t he ability of these agents to induce the release of 5-HT in cultured f etal raphe neurons. The data indicate that the rank order of release p otencies for these agents was (+/-)PCA > (+)MDMA = (+)MDA = (I)FEN. St udies examining the role of calcium in 5-HT release demonstrate that p reventing calcium influx with L- and N-type calcium channel blockers i nhibits potassium-stimulated release of [H-3]5-HT but has no effect on release induced by the substituted amphetamines. Furthermore, omittin g calcium from the extracellular media or depleting the vesicular pool of neurotransmitter with continual potassium stimulation did not affe ct the release of [H-3]5-HT induced by these compounds. Administration of fluoxetine prior to the substituted amphetamines significantly att enuated the releasing effects of these agents, while producing no effe ct on potassium-stimulated release. These results are consistent with the notion that the amphetamines induce release of cytoplasmic 5-HT vi a the plasma membrane transporter.