Cocaine-conditioned place preference by dopamine-deficient mice is mediated by serotonin.
Rodents learn to associate the rewarding effects of drugs with the environment in which they are encountered and, subsequently, will display a conditioned place preference (CPP) for that environment. Cocaine-induced CPP is generally thought to be mediated through inhibition of the dopamine transporter and the consequent increase in extracellular dopamine. However, here we report that dopamine-deficient (DD) mice formed a CPP for cocaine that was not blocked by a dopamine D1-receptor antagonist. Fluoxetine, a serotonin transporter (SERT) inhibitor, produced CPP in DD, but not control mice, suggesting that serotonin mediates cocaine CPP in DD mice. Inhibition of dopamine neuron firing by pretreatment with quinpirole, a dopamine D2-receptor agonist, blocked both cocaine- and fluoxetine-induced CPP in DD mice. These findings are consistent with the hypothesis that, in the absence of dopamine, cocaine-mediated SERT blockade activates dopamine neurons, which then release some other neurotransmitter that contributes to cocaine reward in DD mice.
Hnasko
Thomas S
TS
Graduate Program in Neurobiology and Behavior, University of Washington, Seattle, Washington 98195, USA.
Sotak
Bethany N
BN
Palmiter
Richard D
RD
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects* / Q000235:genetics; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000235:genetics*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism; D012201:Reward; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics
D003042:Cocaine; D004298:Dopamine; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D005473:Fluoxetine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors