Cocaine-Conditioned Place Preference by Dopamine-Deficient Mice Is Mediated by Serotonin
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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 D 1 -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 D 2 -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.
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The involvement of non-dopaminergic neurotransmitters in drug reward is made evident by studies in dopamine-deficient mice, that are still able to show conditioned place preference for cocaine or for morphine.
“The involvement of non- dopaminergic neurotransmitters in drug reward is made evident by studies in dopamine- deficient mice, that are still able to show conditioned place preference for cocaine or for morphine 43 .”
From Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention (2023) · cites this paper as [43]
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- Authors
- Hnasko, T. S., Sotak, B. N., & Palmiter, R. D.
- Affiliations
- University of Washington (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Palmiter, Richard D.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-11-14
- Volume
- 27
- Issue
- 46
- Pages
- 12484-12488
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6673324
- OpenAlex
- W2018966150
- Cited by
- 99
- References
- 37
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 1 · 2018: 5 · 2017: 4 · 2016: 7 · 2015: 4 · 2014: 7 · 2013: 8 · 2012: 8
- FWCI
- 4.25
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (NRSA T32, GM-07270)
- National Institute on Drug Abuse (P50-DA13410)
- National Institute of General Medical Sciences (GM-07270, T32-GM07270, T32GM007270)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- cocaine, conditioned place preference, dopamine deficiency, serotonin, serotonin transporter, fluoxetine, dopamine D1 receptor, dopamine D2 receptor, quinpirole, dopaminergic neurons, drug reward, dopamine transporter
- MeSH terms
- Animals, Brain, Brain Chemistry, Cocaine, Conditioning, Psychological, Disease Models, Animal, Dopamine, Female, Fluoxetine, Male, Mice, Transgenic, Synaptic Transmission, Reward, Serotonin, Selective Serotonin Reuptake Inhibitors, Receptors, Dopamine D1, Receptors, Dopamine D2, Mice, Knockout, Dopamine Agonists, Dopamine Antagonists, Dopamine Uptake Inhibitors, Cocaine-Related Disorders, Serotonin Plasma Membrane Transport Proteins, Mice
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