RESERPINE INHIBITS AMPHETAMINE ACTION IN VENTRAL MIDBRAIN CULTURE

Although amphetamine releases catecholamines from isolated secretory v esicles, a number of in vivo experiments have indicated that the vesic ular amine transport blocker reserpine does not block amphetamine-indu ced release. To address this paradox, we examined the effect of reserp ine on amphetamine-induced dopamine release from postnatal ventral mid brain neurons in culture. These cultures provide a preparation in whic h intracellular, extracellular, and releasable dopamine pools can be m easured simultaneously. We found that 1 mu M reserpine for 90 min redu ced stimulation-dependent dopamine release by >95%. In parallel, reser pine reduced amphetamine-induced dopamine release by >95% compared wit h cells not exposed to reserpine or by 75% compared with reserpine-tre ated cultures. This shows that amphetamine acts principally by redistr ibuting dopamine from synaptic vesicles to the cytosol.