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.
Sulzer
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D
Department of Psychiatry, Columbia University, New York, New York 10032, USA.
St Remy
C
C
Rayport
S
S
D000661:Amphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D007700:Kinetics; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D012110:Reserpine / Q000494:pharmacology*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology*
D012110:Reserpine; D000661:Amphetamine; D004298:Dopamine