Cocaine does not produce reward in absence of dopamine transporter inhibition

Neuroreport. 2009 Jan 7;20(1):9-12. doi: 10.1097/WNR.0b013e32831b9ce4.

Abstract

We have previously reported that knockin mice with a cocaine-insensitive dopamine transporter (DAT-CI mice) do not experience cocaine reward, as measured by conditioned place preference. This conclusion has come under scrutiny because some genetically modified mice show cocaine-induced conditioned place preference in a narrow dose range, that is, responding at doses around 10 mg/kg, but not at 5 and 20 mg/kg, the doses we tested in DAT-CI mice. These results raise the possibility that we have missed the optimal dose for cocaine response. Here we report that cocaine does not produce reward in DAT-CI mice at low, moderate, and high doses, including 10 mg/kg. This study strengthens our conclusion that DAT inhibition is required for cocaine reward in mice with a functional dopaminergic system.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Behavior, Addictive / psychology
  • Cocaine / administration & dosage
  • Cocaine / pharmacology*
  • Conditioning, Psychological / drug effects
  • Conditioning, Psychological / physiology
  • Dopamine Plasma Membrane Transport Proteins / deficiency
  • Dopamine Plasma Membrane Transport Proteins / genetics
  • Dopamine Plasma Membrane Transport Proteins / physiology*
  • Dopamine Uptake Inhibitors / administration & dosage
  • Dopamine Uptake Inhibitors / pharmacology
  • Dose-Response Relationship, Drug
  • Injections, Intraperitoneal
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Reward*

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • Dopamine Uptake Inhibitors
  • Cocaine