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

American Association for the Advancement of Science (AAAS) - Tập 315 Số 5816 - Trang 1267-1270 - 2007
Jeffrey W. Dalley1,2,3,4,5, Tim D. Fryer2,3,4,5, Laurent Brichard1,2,3,4,5, Emma Robinson1,2,3,4,5, David E. H. Theobald1,2,3,4,5, Kristjan Lääne1,2,3,4,5, Yolanda Peña1,2,3,4,5, Emily R. Murphy1,2,3,4,5, Yasmene B. Shah2,3,4,4,5, Katrin C. Probst2,3,4,5, Irina Abakumova2,3,4,5, Franklin I. Aigbirhio2,3,4,5, Richard Edwards2,3,4,5, Young T. Hong2,3,4,5, Jean‐Claude Baron2,6,3,4,5, Barry J. Everitt1,2,3,4,5, Trevor W. Robbins1,2,3,4,5
1Behavioral and Clinical Neuroscience Institute, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK.
2Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK
3Neurosurgery Unit, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
4Sir Peter Mansfield Magnetic Resonance Centre, School of Physics and Astronomy, University of Nottingham, Nottingham NG7 2RD, UK
5Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
6Neurology Unit, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK

Tóm tắt

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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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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American Association for the Advancement of Science (AAAS)

Tập 315 Số 5816

1267-1270

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