Cocaine increases dopamine uptake and cell surface expression of dopamine transporters

Biochem Biophys Res Commun. 2002 Feb 8;290(5):1545-50. doi: 10.1006/bbrc.2002.6384.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anesthetics, Intravenous / administration & dosage
  • Animals
  • Bacterial Proteins / biosynthesis
  • Bacterial Proteins / genetics
  • Cell Line
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cocaine / pharmacology*
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Dopamine / genetics
  • Dopamine / pharmacokinetics*
  • Dopamine Plasma Membrane Transport Proteins
  • Dose-Response Relationship, Drug
  • Electrochemistry
  • Humans
  • Luminescent Proteins / biosynthesis
  • Luminescent Proteins / genetics
  • Male
  • Membrane Glycoproteins / biosynthesis*
  • Membrane Glycoproteins / pharmacokinetics
  • Membrane Transport Proteins / biosynthesis*
  • Membrane Transport Proteins / pharmacokinetics
  • Nerve Tissue Proteins*
  • Rats
  • Rats, Sprague-Dawley
  • Synaptosomes / metabolism
  • Transfection
  • Tritium / pharmacokinetics
  • Up-Regulation / drug effects
  • Up-Regulation / genetics

Substances

  • Anesthetics, Intravenous
  • Bacterial Proteins
  • Dopamine Plasma Membrane Transport Proteins
  • Luminescent Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • SLC6A3 protein, human
  • Slc6a3 protein, rat
  • yellow fluorescent protein, Bacteria
  • Tritium
  • Cocaine
  • Dopamine