Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Nucleus Accumbens D2/3 Receptors Predict Trait Impulsivity and Cocaine Reinforcement
Jeffrey W. Dalley,1,2*Tim D. Fryer,1,3Laurent Brichard,1Emma S. J. Robinson,1David E. H. Theobald,1,2Kristjan Lääne,1,2Yolanda Peña,1Emily R. Murphy,1,2Yasmene Shah,4Katrin Probst,1,3Irina Abakumova,1,3Franklin I. Aigbirhio,1,3Hugh K. Richards,1,5Young Hong,1,3Jean-Claude Baron,1,6Barry J. Everitt,1,2Trevor W. Robbins1,2
Stimulant addiction is often linked to excessive risk taking,sensation seeking, and impulsivity, but in ways that are poorlyunderstood. We report here that a form of impulsivity in ratspredicts high rates of intravenous cocaine self-administrationand is associated with changes in dopamine (DA) function beforedrug exposure. Using positron emission tomography, we demonstratedthat D2/3 receptor availability is significantly reduced inthe nucleus accumbens of impulsive rats that were never exposedto cocaine and that such effects are independent of DA release.These data demonstrate that trait impulsivity predicts cocainereinforcement and that D2 receptor dysfunction in abstinentcocaine 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.
Present address: Laboratoire d'Imagerie Moléculaire etFonctionnelle: de la Physiologie à la Thérapie,ERT CNRS/Université Victor Segalen Bordeaux 2, Bordeaux,France.
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
The editors suggest the following Related Resources on Science sites:
In Science Magazine
LETTERS
John C. Crabbe, Christopher L. Cunningham;, Jeffrey W. Dalley, Barry J. Everitt, and Trevor W. Robbins (24 August 2007) Science317 (5841), 1033.
[DOI: 10.1126/science.317.5841.1033] |Full Text »|PDF »
In Science Signaling
EDITORS' CHOICE
Peter Stern (6 March 2007) Sci. STKE2007 (376), tw79.
[DOI: 10.1126/stke.3762007tw79] |Abstract »
W. K. Schiffer, C. N. B. Liebling, C. Reiszel, J. M. Hooker, J. D. Brodie, and S. L. Dewey (2009)
J. Neurosci.
29, 6176-6185
|Abstract »|Full Text »|PDF »
Increased striatal dopamine release in Parkinsonian patients with pathological gambling: a [11C] raclopride PET study.
T. D. L. Steeves, J. Miyasaki, M. Zurowski, A. E. Lang, G. Pellecchia, T. Van Eimeren, P. Rusjan, S. Houle, and A. P. Strafella (2009)
Brain
132, 1376-1385
|Abstract »|Full Text »|PDF »
Dopamine Release in Dissociable Striatal Subregions Predicts the Different Effects of Oral Methylphenidate on Reversal Learning and Spatial Working Memory.
P. L. Clatworthy, S. J. G. Lewis, L. Brichard, Y. T. Hong, D. Izquierdo, L. Clark, R. Cools, F. I. Aigbirhio, J.-C. Baron, T. D. Fryer, et al. (2009)
J. Neurosci.
29, 4690-4696
|Abstract »|Full Text »|PDF »
A Role for the Endocannabinoid System in the Increased Motivation for Cocaine in Extended-Access Conditions.
L. Orio, S. Edwards, O. George, L. H. Parsons, and G. F. Koob (2009)
J. Neurosci.
29, 4846-4857
|Abstract »|Full Text »|PDF »
Dopamine DRD2 Polymorphism Alters Reversal Learning and Associated Neural Activity.
G. Jocham, T. A. Klein, J. Neumann, D. Y. von Cramon, M. Reuter, and M. Ullsperger (2009)
J. Neurosci.
29, 3695-3704
|Abstract »|Full Text »|PDF »
From observation to experimentation: leptin action in the mediobasal hypothalamus.
K. W Williams, M. M Scott, and J. K Elmquist (2009)
Am. J. Clinical Nutrition
89, 985S-990S
|Abstract »|Full Text »|PDF »
Increased Impulsivity during Withdrawal from Cocaine Self-Administration: Role for {Delta}FosB in the Orbitofrontal Cortex.
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)
Cereb Cortex
19, 435-444
|Abstract »|Full Text »|PDF »
Introduction. The neurobiology of drug addiction: new vistas.
T.W Robbins, B.J Everitt, and D.J Nutt (2008)
Phil Trans R Soc B
363, 3109-3111
|Full Text »|PDF »
Neural mechanisms underlying the vulnerability to develop compulsive drug-seeking habits and addiction.
B. J Everitt, D. Belin, D. Economidou, Y. Pelloux, J. W Dalley, and T. W Robbins (2008)
Phil Trans R Soc B
363, 3125-3135
|Abstract »|Full Text »|PDF »
The neurobiology of pathological gambling and drug addiction: an overview and new findings.
Present address: Laboratoire d'Imagerie Moléculaire et Fonctionnelle: de la Physiologie à la Thérapie, ERT CNRS/Université Victor Segalen Bordeaux 2, Bordeaux, France. 
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. 
