Cited by 1,188Neurotransmitter Receptor Influence on BehaviorNeural and Behavioral Psychology StudiesSubstance Abuse Treatment and Outcomes

Nucleus accumbens D2/3 receptors predict trait impulsivity and cocaine reinforcement

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Dalley, Jeffrey W., Fryer, Tim D., Brichard, Laurent, Robinson, Emma S. J., Theobald, David E. H., Lääne, Kristjan, Peña, Yolanda, Murphy, Emily R. +9 more·2007·Science

Abstract

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.”
  • 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).”
  • 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).”
  • 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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Research works printed but not linked: 2

  1. [46]Paxinos G Watson C The Rat Brain in Stereotaxic Coordinates 1998 xxvi San Diego, CA Academic Press ed. 4
  2. [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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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.
Venue
Science
Published
2007-03-02
Volume
315
Issue
5816
Pages
1267-1270
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
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
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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