Cocaine increases dopamine uptake and cell surface expression of dopamine transporters |
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Authors: | Daws Lynette C Callaghan Paul D Morón José A Kahlig Kris M Shippenberg Toni S Javitch Jonathan A Galli Aurelio |
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Affiliation: | Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MC 7764, San Antonio, Texas 78229-3900, USA. |
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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. |
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Keywords: | cocaine dopamine transporter trafficking uptake biotinylation chronoamperometry striatum nucleus accumbens |
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