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Cocaine increases dopamine uptake and cell surface expression of dopamine transporters.

Daws LC, Callaghan PD, Morón JA, Kahlig KM, Shippenberg TS, Javitch JA, Galli A
Biochem Biophys Res Commun. 2002 290 (5): 1545-50

PMID: 11820798 · DOI:10.1006/bbrc.2002.6384

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).

MeSH Terms (23)

Anesthetics, Intravenous Animals Bacterial Proteins Cell Line Cell Membrane Cocaine Corpus Striatum Dopamine Dopamine Plasma Membrane Transport Proteins Dose-Response Relationship, Drug Electrochemistry Humans Luminescent Proteins Male Membrane Glycoproteins Membrane Transport Proteins Nerve Tissue Proteins Rats Rats, Sprague-Dawley Synaptosomes Transfection Tritium Up-Regulation

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