Cocaine self-administration in dopamine-transporter knockout mice.
The plasma membrane dopamine transporter (DAT) is responsible for clearing dopamine from the synapse. Cocaine blockade of DAT leads to increased extracellular dopamine, an effect widely considered to be the primary cause of the reinforcing and addictive properties of cocaine. In this study we tested whether these properties are limited to the dopaminergic system in mice lacking DAT. In the absence of DAT, these mice exhibit high levels of extracellular dopamine, but paradoxically still self-administer cocaine. Mapping of the sites of cocaine binding and neuronal activation suggests an involvement of serotonergic brain regions in this response. These results demonstrate that the interaction of cocaine with targets other than DAT, possibly the serotonin transporter, can initiate and sustain cocaine self-administration in these mice.
Rocha
B A
BA
Department of Pharmacology, University of North Texas Health Science Center, Fort Worth 76107, USA.
Fumagalli
F
F
Gainetdinov
R R
RR
Jones
S R
SR
Ator
R
R
Giros
B
B
Miller
G W
GW
Caron
M G
MG
D000818:Animals; D001665:Binding Sites / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics*; D003042:Cocaine / Q000008:administration & dosage*; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics* / Q000502:physiology*; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012646:Self Administration; D012701:Serotonin / Q000502:physiology
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; C493215:Slc6a3 protein, mouse; D012701:Serotonin; D003042:Cocaine; D004298:Dopamine