INTEGRATIVE TRANSPORTER-MEDIATED RELEASE FROM CYTOPLASMIC AND VESICULAR 5-HYDROXYTRYPTAMINE STORES IN CULTURED NEURONS

The direct effects of 3,4-methylenedioxymethamphetamine (MDMA) and p-c hloroamphetamine (PCA) were studied in microculture of fetal 5-hydroxy tryptamine (5-HT) neurons. Both MDMA and PCA released 5-HT with the po tency of PCA > MDMA by a mechanism inhibited by fluoxetine, an inhibit or of the 5-HT transporter. The transporter-mediated release by MDMA a nd PCA reduced intracellular stores of 5-HT. Both MDMA and PCA inhibit MAO-A activities, which also contributes to the increase of extracell ular 5-HT levels. Deprenyl (10(-7) M) increased the amount of intracel lular 5-HT and potentiated the MDMA- or PCA-induced release of 5-HT. C onversely, reserpine (10(-9) M) reduced the intracellular 5-HT levels and attenuated the transporter-mediated release. In addition, MDMA- or PCA-mediated release was attenuated by nimodipine (10(-8) M), an L-ty pe Ca2+ channel antagonist. Our results indicate that MDMA- or PCA-ind uced release of 5-HT occurs from the cytoplasm to the media through th e 5-HT transporter, and that the release may incorporate 5-HT from the vesicular stores.