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Journal of Neuroscience, Vol 15, 4102-4108, Copyright © 1995 by Society for Neuroscience
Amphetamine redistributes dopamine from synaptic vesicles to the cytosol and promotes reverse transport
D Sulzer, TK Chen, YY Lau, H Kristensen, S Rayport and A Ewing
Department of Psychiatry, Columbia University, New York, New York 10032, USA.
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.
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