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Dopamine Neuronal Transport Kinetics and Effects of Amphetamine
Author(s) -
Jones Sara R.,
Joseph Joshua D.,
Barak Larry S.,
Caron Marc G.,
Wightman R. Mark
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0732406.x
Subject(s) - amphetamine , nomifensine , chemistry , extracellular , dopamine , dopamine transporter , veratridine , catecholamine , dopamine plasma membrane transport proteins , endocrinology , medicine , intracellular , biophysics , mazindol , pharmacology , sodium , biochemistry , sodium channel , biology , dopaminergic , organic chemistry
: The dopamine (DA) transporter (DAT) regulates DA neurotransmission by recycling DA back into neurons. Drugs that interfere with DAT function, e.g., cocaine and amphetamine, can have profound behavioral effects. The kinetics of DA transport by DAT in isolated synaptosomal or single cell preparations have been previously studied. To investigate how DA transport is regulated in intact tissue and to examine how amphetamine affects the DAT, the kinetics of DA uptake by the DAT were examined in tissue slices of the mouse caudate‐putamen with fastscan cyclic voltammetry. The data demonstrate that inward DA transport is saturable and sodium‐dependent. Elevated levels of cytoplasmic DA resulting from disruption of vesicular storage by incubation with 10 μ M Ro 4‐1284 did not generate DA efflux or decrease its uptake rate. However, incubation with 10 μ M amphetamine reduced the net DA uptake rate and increased extracellular DA levels due to DA efflux through the DAT. In addition, a new, elevated steady‐state level of extracellular DA was established after electrically stimulated DA release in the presence of amphetamine, norepinephrine, and exogenous DA. These results from intact tissue are consistent with a kinetic model of the DAT established in more purified preparations in which amphetamine and other transported substances make the inwardly facing DAT available for outward transport of intracellular DA.