Abstract

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