Reserpine inhibits amphetamine action in ventral midbrain culture

Although amphetamine releases catecholamines from isolated secretory vesicles, a number of in vivo experiments have indicated that the vesicular amine transport blocker reserpine does not block amphetamine-induced release. To address this paradox, we examined the effect of reserpine on amphetamine-induced dopamine release from postnatal ventral midbrain neurons in culture. These cultures provide a preparation in which intracellular, extracellular, and releasable dopamine pools can be measured simultaneously. We found that 1 microM reserpine for 90 min reduced stimulation-dependent dopamine release by > 95%. In parallel, reserpine reduced amphetamine-induced dopamine release by > 95% compared with cells not exposed to reserpine or by 75% compared with reserpine-treated cultures. This shows that amphetamine acts principally by redistributing dopamine from synaptic vesicles to the cytosol.