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Amphetamine releases dopamine from synaptic vesicles by dual mechanisms
1Department of Physiology and Cell Biology, University of Kansas, Lawrence 66045, USA. floor@smissman.hbc.ukans.edu
Neuroscience Letters
|August 30, 1996
Summary
D-amphetamine (AMPH) releases dopamine (DA) from synaptic vesicles via different mechanisms depending on concentration. Low AMPH concentrations inhibit dopamine uptake, while high concentrations disrupt the proton gradient, causing rapid dopamine release.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Dopamine (DA) is a key neurotransmitter involved in reward and motor control.
- Synaptic vesicles store and release DA into the synaptic cleft.
- D-amphetamine (AMPH) is a psychostimulant known to affect DA levels.
Purpose of the Study:
- To investigate the mechanisms by which D-amphetamine (AMPH) releases dopamine (DA) from rat brain synaptic vesicles.
- To differentiate the effects of low and high concentrations of AMPH on DA release.
Main Methods:
- Purified rat brain synaptic vesicles were used.
- The release of [3H]dopamine (DA) was measured.
- Kinetics and half-times of DA release were determined.
- The role of vesicle alkalinization and proton gradients was assessed.
Main Results:
- Low AMPH concentrations caused DA release with exponential kinetics (half-time of 4 min), likely via inhibition of DA uptake followed by release through an independent pathway.
- High AMPH concentrations severely reduced the vesicle proton gradient, leading to rapid DA release (half-time < 1 min).
- Loss of the proton gradient was sufficient to explain DA release at high AMPH concentrations.
Conclusions:
- D-amphetamine (AMPH) releases dopamine (DA) from synaptic vesicles through distinct mechanisms at low and high concentrations.
- Low AMPH concentrations appear to utilize an uptake-dependent, then release pathway.
- High AMPH concentrations directly impact the vesicular proton gradient, driving DA efflux.