Abstract
In HEK 293 cells expressing the human dopamine transporter (DAT), a 10-min incubation with 10 microM cocaine followed by extensive washing resulted in a 30% increase in [3H]dopamine (DA) uptake as well as an increase in cell surface DAT in biotinylation experiments. Consistent with this novel regulation, [3H]DA uptake into synaptosomes prepared from the nucleus accumbens of rats sacrificed 30 min after a single cocaine injection (30 mg/kg) was significantly increased compared to controls (56% increase in V(max), no change in K(m)). In addition, DA clearance in the striatum of anesthetized rats was increased after local application of a low (3 pmol) but not high (65 pmol) dose of cocaine, presumably as a result of mobilization of DAT to the cell surface. Cocaine-induced increases in cell surface expression of DAT and associated changes in DA clearance represent a novel mechanism that may play a role in its addictive properties.
©2002 Elsevier Science (USA).
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Anesthetics, Intravenous / administration & dosage
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Animals
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Bacterial Proteins / biosynthesis
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Bacterial Proteins / genetics
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Cell Line
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Cell Membrane / drug effects
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Cell Membrane / metabolism
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Cocaine / pharmacology*
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Corpus Striatum / drug effects
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Corpus Striatum / metabolism
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Dopamine / genetics
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Dopamine / pharmacokinetics*
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Dopamine Plasma Membrane Transport Proteins
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Dose-Response Relationship, Drug
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Electrochemistry
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Humans
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Luminescent Proteins / biosynthesis
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Luminescent Proteins / genetics
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Male
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Membrane Glycoproteins / biosynthesis*
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Membrane Glycoproteins / pharmacokinetics
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Membrane Transport Proteins / biosynthesis*
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Membrane Transport Proteins / pharmacokinetics
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Nerve Tissue Proteins*
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Rats
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Rats, Sprague-Dawley
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Synaptosomes / metabolism
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Transfection
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Tritium / pharmacokinetics
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Up-Regulation / drug effects
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Up-Regulation / genetics
Substances
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Anesthetics, Intravenous
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Bacterial Proteins
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Dopamine Plasma Membrane Transport Proteins
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Luminescent Proteins
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Membrane Glycoproteins
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Membrane Transport Proteins
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Nerve Tissue Proteins
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SLC6A3 protein, human
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Slc6a3 protein, rat
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yellow fluorescent protein, Bacteria
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Tritium
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Cocaine
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Dopamine