Cocaine does not produce reward in absence of dopamine transporter inhibition.
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.
Tilley
Michael R
MR
Department of aPharmacology, Ohio State University College of Medicine, Columbus, Ohio 43210, USA.
O'Neill
Brian
B
Han
Dawn D
DD
Gu
Howard H
HH
D000818:Animals; D016739:Behavior, Addictive / Q000523:psychology; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012201:Reward
D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D003042:Cocaine