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Cerebral Cortex Advance Access published online on August 18, 2009
Cerebral Cortex, doi:10.1093/cercor/bhp167
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© The Author 2009. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Dopamine Receptor D1/D5 Gene Expression in the Medial Prefrontal Cortex Predicts Impulsive Choice in Rats

Maarten Loos1, Tommy Pattij2, Mieke C. W. Janssen2, Danielle S. Counotte1, Anton N. M. Schoffelmeer2, August B. Smit1, Sabine Spijker1 and Marcel M. van Gaalen2,3

1 Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands, 2 Department of Anatomy and Neurosciences, Center for Neurogenomics and Cognitive Research, VU University Medical Center, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands, 3 Current address: Neuroscience Research, GPRD, Abbott, Knollstrasse 50, D-67061 Ludwigshafen, Germany

Address correspondence to Sabine Spijker, Department of Molecular & Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands. Email: sabine.spijker{at}cncr.vu.nl.

A neuropsychological hallmark of attention deficit/hyperactivity disorder (ADHD) is the reduced ability to tolerate delay of reinforcement, leading to impulsive choice. Genetic association studies have implicated several genes involved in dopaminergic neurotransmission in ADHD. In this study, we investigated whether differences in the expression level of these dopamine-related genes of rats predict the individual level of impulsive choice. Among all frontostriatal brain regions tested, only in the medial prefrontal cortex (mPFC), we observed significant positive correlations between impulsive choice and transcript levels of the dopamine receptor D1, the dopamine receptor D5 and calcyon. Local mPFC infusions of the D1/D5 receptor antagonist SCH 23390 and agonist SKF 38393 resulted in increased impulsive choice, in agreement with the idea that endogenous receptor D1/D5 stimulation in the mPFC promotes the choice of large delayed rewards. Together, these data indicate that this class of dopamine receptors in the mPFC plays a pivotal role in impulsive choice, and aberrancies thereof might contribute to ADHD symptomatology.

Key Words: caly • Drd1 • Drd5 • impulsive decision making • real-time quantitative polymerase chain reaction

Sabine Spijker and Marcel M. van Gaalen have contributed equally to this work.


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