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Critical Involvement of Dopaminergic Neurotransmission in Impulsive Decision Making

  • Marcel M. van Gaalen
    Correspondence
    Address reprint requests to Dr. M.M. van Gaalen, Abbott GmbH & Co KG, CNS Pharmacology, P.O. Box 210805, 67008 Ludwigshafen, Germany
    Affiliations
    Department of Medical Pharmacology, Research Institute Neurosciences Vrije Universiteit, Center for Neurogenomics and Cognitive Research, Free University Medical Center, Amsterdam, The Netherlands.
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  • Reinout van Koten
    Affiliations
    Department of Medical Pharmacology, Research Institute Neurosciences Vrije Universiteit, Center for Neurogenomics and Cognitive Research, Free University Medical Center, Amsterdam, The Netherlands.
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  • Anton N.M. Schoffelmeer
    Affiliations
    Department of Medical Pharmacology, Research Institute Neurosciences Vrije Universiteit, Center for Neurogenomics and Cognitive Research, Free University Medical Center, Amsterdam, The Netherlands.
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  • Louk J.M.J. Vanderschuren
    Affiliations
    Department of Medical Pharmacology, Research Institute Neurosciences Vrije Universiteit, Center for Neurogenomics and Cognitive Research, Free University Medical Center, Amsterdam, The Netherlands.
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      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 α2 adrenoceptor agonist clonidine increased impulsivity, but the α1 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.

      Key Words

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