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Science 315 (5816): 1267-1270

Copyright © 2007 by the American Association for the Advancement of Science

Nucleus Accumbens D2/3 Receptors Predict Trait Impulsivity and Cocaine Reinforcement

Jeffrey W. Dalley,1,2* Tim D. Fryer,1,3 Laurent Brichard,1{dagger} Emma S. J. Robinson,1{ddagger} David E. H. Theobald,1,2 Kristjan Lääne,1,2 Yolanda Peña,1§ Emily R. Murphy,1,2 Yasmene Shah,4 Katrin Probst,1,3 Irina Abakumova,1,3 Franklin I. Aigbirhio,1,3 Hugh K. Richards,1,5 Young Hong,1,3 Jean-Claude Baron,1,6 Barry J. Everitt,1,2 Trevor W. Robbins1,2

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.

1 Behavioral and Clinical Neuroscience Institute, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK.
2 Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK.
3 Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK.
4 Sir Peter Mansfield Magnetic Resonance Centre, School of Physics and Astronomy, University of Nottingham, Nottingham NG7 2RD, UK.
5 Neurosurgery Unit, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK.
6 Neurology Unit, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK.

{dagger} Present address: Laboratoire d'Imagerie Moléculaire et Fonctionnelle: de la Physiologie à la Thérapie, ERT CNRS/Université Victor Segalen Bordeaux 2, Bordeaux, France.

{ddagger} Present address: Department of Pharmacology, University of Bristol, Bristol BS8 1TD, UK.

§ Present address: Departament de Psiquiatria i de Medicina Legal, Universita Autònoma de Barcelona, Barcelona, Spain.

* To whom correspondence should be addressed. E-mail: jwd20{at}cam.ac.uk

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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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C. A. Winstanley, R. K. Bachtell, D. E.H. Theobald, S. Laali, T. A. Green, A. Kumar, S. Chakravarty, D. W. Self, and E. J. Nestler (2009)
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   Abstract »    Full Text »    PDF »
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   Full Text »    PDF »
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B. J Everitt, D. Belin, D. Economidou, Y. Pelloux, J. W Dalley, and T. W Robbins (2008)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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M. A Nader, P. W Czoty, R. W Gould, and N. V Riddick (2008)
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   Abstract »    Full Text »    PDF »
Acute effects of cocaine on the neurobiology of cognitive control.
H. Garavan, J. N Kaufman, and R. Hester (2008)
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   Abstract »    Full Text »    PDF »
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Neuroscientist 14, 381-395
   Abstract »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »

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