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The Journal of Neuroscience, November 14, 2007, 27(46):12484-12488; doi:10.1523/JNEUROSCI.3133-07.2007

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Brief Communications
Cocaine-Conditioned Place Preference by Dopamine-Deficient Mice Is Mediated by Serotonin

Thomas S. Hnasko,^1 * Bethany N. Sotak,^2 * and Richard D. Palmiter²

¹Graduate Program in Neurobiology and Behavior and ²Howard Hughes Medical Institute and Department of Biochemistry, University of Washington, Seattle, Washington 98195

Correspondence should be addressed to Richard D. Palmiter, Howard Hughes Medical Institute, Box 357370, University of Washington, Seattle, WA 98195. Email: palmiter{at}u.washington.edu

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.

Key words: cocaine; conditioned place preference; dopamine; dopamine-deficient; dopamine transporter; serotonin transporter

---

Received July 10, 2007; revised Sept. 11, 2007; accepted Oct. 2, 2007.

Correspondence should be addressed to Richard D. Palmiter, Howard Hughes Medical Institute, Box 357370, University of Washington, Seattle, WA 98195. Email: palmiter{at}u.washington.edu

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