Critical involvement of dopaminergic neurotransmission in impulsive decision making.
BACKGROUND
Impulsive decision making, apparent as intolerance for reinforcement delay, is prominent in attention-deficit/hyperactivity disorder. Commonly prescribed for this condition, amphetamine (Adderall), reduces impulsive decision making; however, the neuropharmacologic mechanism of this effect of amphetamine is unclear.


METHODS
We investigated the involvement of dopaminergic and noradrenergic neurotransmission in impulsive decision making in rats, using a delayed reward task.


RESULTS
Amphetamine and methylphenidate decreased impulsive decision making, which was mimicked by the selective dopamine reuptake inhibitor GBR 12909 but not by the noradrenaline reuptake inhibitor desipramine. Impulsive choice was increased by the dopamine D1 receptor antagonist SCH-23390 but not the dopamine D2 receptor antagonist eticlopride. The effect of amphetamine on impulsive choice was attenuated by pretreatment with eticlopride, whereas amphetamine retained its effect on impulsivity in the presence of SCH-23390. The alpha2 adrenoceptor agonist clonidine increased impulsivity, but the alpha1 adrenoceptor agonist phenylephrine did not affect impulsive decision making.


CONCLUSIONS
These data demonstrate an important role for dopaminergic neurotransmission in impulsive decision making, whereby tolerance to delay of reinforcement depends on dopamine D1 receptor activation. Activation of dopamine D2 receptors appears to mediate the beneficial effects of amphetamine on impulsive behavior. Noradrenergic neurotransmission may play a minor role in impulsive choice.
van Gaalen
Marcel M
MM
Department of Medical Pharmacology, Research Institute Neurosciences Vrije Universiteit, Center for Neurogenomics and Cognitive Research, Free University Medical Center, Amsterdam, The Netherlands. marcel.vangaalen@abottt.com
van Koten
Reinout
R
Schoffelmeer
Anton N M
AN
Vanderschuren
Louk J M J
LJ
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology*; D003000:Clonidine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007175:Impulsive Behavior / Q000503:physiopathology*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012201:Reward
D018759:Adrenergic Uptake Inhibitors; D000316:Adrenergic alpha-Agonists; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D010656:Phenylephrine; D003000:Clonidine; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine