Cocaine increases dopamine uptake and cell surface expression of dopamine transporters

Lynette C. Daws, Paul D. Callaghan, José A. Morón, Kris M. Kahlig, Aurelio Galli, José A. Morón, Toni S. Shippenberg, Jonathan A. Javitch

Research output: Contribution to journalArticlepeer-review

137 Scopus citations

Abstract

In HEK 293 cells expressing the human dopamine transporter (DAT), a 10-min incubation with 10 μM 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 Vmax, no change in Km). 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.

Original languageEnglish (US)
Pages (from-to)1545-1550
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume290
Issue number5
DOIs
StatePublished - 2002

Keywords

  • Biotinylation
  • Chronoamperometry
  • Cocaine
  • Dopamine transporter
  • Nucleus accumbens
  • Striatum
  • Trafficking
  • Uptake

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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