Dopamine D2/3- and μ-opioid receptor antagonists reduce cue-induced responding and reward impulsivity in humans

Abstract

Increased responding to drug-associated stimuli (cue reactivity) and an inability to tolerate delayed gratification (rewardimpulsivity) have been implicated in the development and maintenance of drug addiction. Whereas data from animal studiessuggest that both the dopamine and opioid system are involved in these two reward-related processes, their role in humans is lessclear. Moreover, dopaminergic and opioidergic drugs have not been directly compared with regard to these functions, even thougha deeper understanding of the underlying mechanisms might inform the development of specific treatments for elevated cuereactivity and reward impulsivity. In a randomized, double-blind, between-subject design we administered the selective dopamineD2/D3 receptor antagonist amisulpride (400 mg,n= 41), the unspecific opioid receptor antagonist naltrexone (50 mg,n= 40) orplacebo (n= 40) to healthy humans and measured cue-induced responding with a Pavlovian-instrumental transfer task and rewardimpulsivity with a delay discounting task. Mood was assessed using a visual analogue scale. Compared with placebo, amisulpridesignificantly suppressed cue-induced responding and reward impulsivity. The effects of naltrexone were similar, although lesspronounced. Both amisulpride and naltrexone decreased average mood ratings compared with placebo. Our results demonstratethat a selective blockade of dopamine D2/D3 receptors reduces cue-induced responding and reward impulsivity in healthy humans.Antagonizingμ-opioid receptors has similar effects for cue-induced responding and to a lesser extent for reward impulsivity.