Nucleus accumbens D2/3 receptors predict trait impulsivity and cocaine reinforcement
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Stimulant addiction is often linked to excessive risk taking, sensation seeking, and impulsivity, but in ways that are poorly understood. We report here that a form of impulsivity in rats predicts high rates of intravenous cocaine self-administration and is associated with changes in dopamine (DA) function before drug exposure. Using positron emission tomography, we demonstrated that D2/3 receptor availability is significantly reduced in the nucleus accumbens of impulsive rats that were never exposed to cocaine and that such effects are independent of DA release. These data demonstrate that trait impulsivity predicts cocaine reinforcement and that D2 receptor dysfunction in abstinent cocaine addicts may, in part, be determined by premorbid influences.
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Excessive impulsive responding in the 5-choice Serial Reaction Time Task predicts marked escalation of cocaine self-administration compared with non-impulsive controls.
“Dalley et al. (Dalley et al., 2007) showed that excessive impulsive responding in the 5-choice Serial Reaction Time Task (5CSRTT) predicts marked escalation of cocaine self-administration compared with non-impulsive controls.”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Dalley et al., 2007
D2 receptor availability is reduced in the nucleus accumbens of impulsive rats.
“Using PET and autoradiography, previous studies have shown that D2 receptor availability is reduced in the nucleus accumbens of impulsive rats (Dalley et al., 2007; Jupp et al., 2013; Caprioli et al., 2013).”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Dalley et al., 2007
Animals with low D2 receptor levels in the striatum before drug or alcohol exposure subsequently display greater cocaine or alcohol self-administration.
“Strikingly, animals with low D2 receptor levels in the striatum prior to drug or alcohol exposure subsequently display greater cocaine or alcohol self-administration (Czoty et al., 2004; Dalley et al., 2007; McBride et al., 1993; Morgan et al., 2002; Nader et al., 2006; Stefanini et al., 1992).”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Dalley et al., 2007
Dopamine D2-receptor expression in the dorsal striatum was significantly reduced in parallel to worsening of the reward threshold, to levels found in cocaine-addicted rats.
“Furthermore, dopamine D2-receptor expression in the dorsal striatum was significantly reduced in parallel to worsening of the reward threshold ([89](#B89)), to levels found in cocaine-addicted rats ([35](#B35)).”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [35]
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- [47]This research was supported by a joint award from the U.K. Medical Research Council (MRC) and the Wellcome Trust and by an MRC Pathfinder grant (G0401068) to J.W.D., B.J.E., and T.W.R. D.E.H.T. was supported by the Wellcome Trust. Y.P. was supported by a predoctoral Formación Investigadora scholarship from Generalitat de Catalunya. E.S.J.R. holds a Research Councils UK Academic Fellowship supported by the British Pharmacological Society Integrative Pharmacology Fund. E.R.M. was supported by a Gates Cambridge scholarship. We thank Merck, Sharp, & Dohme for originally donating the micro-PET scanner to Cambridge University.
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“However, in a similar study found that rats with high “impulsivity” showed greater escalation of intravenous cocaine selfadministration (Dalley et al., 2007).”
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- Authors
- Dalley, J. W., Fryer, T. D., Brichard, L., Robinson, E. S. J., Theobald, D. E. H., Lääne, K., Peña, Y., Murphy, E. R., Shah, Y., Probst, K., Abakumova, I., Aigbirhio, F. I., Richards, H. K., Hong, Y., Baron, J.-C., Everitt, B. J., & Robbins, T. W.
- Affiliations
- University of Nottingham (GB)
- Behavioral and Clinical Neuroscience Institute, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK.
- Corresponding author
- Dalley, Jeffrey W.
- Brichard, Laurent
- Robinson, Emma S. J.
- ORCID
- Venue
- Science
- Published
- 2007-03-02
- Volume
- 315
- Issue
- 5816
- Pages
- 1267-1270
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC1892797
- OpenAlex
- W1983332126
- Cited by
- 1,188
- References
- 44
- Citations by year
- 2026: 14 · 2025: 27 · 2024: 40 · 2023: 33 · 2022: 40 · 2021: 42 · 2020: 73 · 2019: 50 · 2018: 56 · 2017: 56 · 2016: 59 · 2015: 77 · 2014: 73 · 2013: 104 · 2012: 93
- FWCI
- 31.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Explore Bristol Research (submittedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Funders
- Wellcome Trust (076244)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- nucleus accumbens, trait impulsivity, cocaine self-administration, cocaine reinforcement, dopaminergic activity, cocaine dependence, risk-taking, sensation seeking
- MeSH terms
- Animals, Basal Ganglia, Benzamides, Cocaine, Corpus Striatum, Dopamine, Impulsive Behavior, Male, Synaptic Transmission, Nucleus Accumbens, Pyrrolidines, Reaction Time, Reinforcement, Psychology, Self Administration, Receptors, Dopamine D2, Dopamine Antagonists, Cocaine-Related Disorders, Positron-Emission Tomography, Receptors, Dopamine D3, Rats
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