Dopamine receptor D1/D5 gene expression in the medial prefrontal cortex predicts impulsive choice in rats.
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 D(1), the dopamine receptor D(5) and calcyon. Local mPFC infusions of the D(1)/D(5) receptor antagonist SCH 23390 and agonist SKF 38393 resulted in increased impulsive choice, in agreement with the idea that endogenous receptor D(1)/D(5) 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.
Loos
Maarten
M
Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands.
Pattij
Tommy
T
Janssen
Mieke C W
MC
Counotte
Danielle S
DS
Schoffelmeer
Anton N M
AN
Smit
August B
AB
Spijker
Sabine
S
van Gaalen
Marcel M
MM
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002755:Choice Behavior / Q000502:physiology*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D007175:Impulsive Behavior / Q000235:genetics*; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D011237:Predictive Value of Tests; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050641:Receptors, Dopamine D5 / Q000235:genetics / Q000378:metabolism*; D012201:Reward; D012702:Serotonin Antagonists / Q000494:pharmacology; D013223:Statistics as Topic
D001552:Benzazepines; D015259:Dopamine Agents; D008565:Membrane Proteins; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D012702:Serotonin Antagonists; C405464:calcyon; D050641:Receptors, Dopamine D5; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D007650:Ketanserin