Amphetamine redistributes dopamine from synaptic vesicles to the cytosol and promotes reverse transport

David Sulzer, Ta Kung Chen, Yau Yi Lau, Helle Kristensen, Stephen Rayport, Andrew Ewing

Research output: Contribution to journalArticlepeer-review

566 Scopus citations

Abstract

Whether amphetamine acts principally at the plasma membrane or at synaptic vesicles is controversial. We find that d-amphetamine injection into the Planorbis giant dopamine neuron causes robust dopamine release, demonstrating that specific amphetamine uptake is not required. Arguing for action at vesicles, whole-cell capillary electrophoresis of single Planorbis dopamine neurons shows that amphetamine reduces vesicular dopamine, while amphetamine reduces quantal dopamine release from PC12 cells by > 50% per vesicle. Intracellular injection of dopamine into the Planorbis dopamine neuron produces rapid nomifensine-sensitive release, showing that an increased substrate concentration gradient is sufficient to induce release. These experiments indicate that amphetamine acts at the vesicular level where it redistributes dopamine to the cytosol, promoting reverse transport, and dopamine release.

Original languageEnglish (US)
Pages (from-to)4102-4108
Number of pages7
JournalJournal of Neuroscience
Volume15
Issue number5 II
DOIs
StatePublished - May 1995

All Science Journal Classification (ASJC) codes

  • General Neuroscience

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