AMPHETAMINE REDISTRIBUTES DOPAMINE FROM SYNAPTIC VESICLES TO THE CYTOSOL AND PROMOTES REVERSE TRANSPORT

Whether amphetamine acts principally at the plasma membrane or at syna ptic vesicles is controversial. We find that d-amphetamine injection i nto the Planorbis giant dopamine neuron causes robust dopamine release , demonstrating that specific amphetamine uptake is not required. Argu ing for action at vesicles, whole-cell capillary electrophoresis of si ngle Planorbis dopamine neurons shows that amphetamine reduces vesicul ar dopamine, while amphetamine reduces quantal dopamine release from P C12 cells by > 50% per vesicle. Intracellular injection of dopamine in to 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 ampheta mine acts at the vesicular level where it redistributes dopamine to th e cytosol, promoting reverse transport, and dopamine release.