title: 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 (reward impulsivity) have been implicated in the development and maintenance of drug addiction. Whereas data from animal studies suggest that both the dopamine and opioid system are involved in these two reward-related processes, their role in humans is less clear. Moreover, dopaminergic and opioidergic drugs have not been directly compared with regard to these functions, even though a deeper understanding of the underlying mechanisms might inform the development of specific treatments for elevated cue reactivity and reward impulsivity. In a randomized, double-blind, between-subject design we administered the selective dopamine D2/D3 receptor antagonist amisulpride (400 mg, n=41), the unspecific opioid receptor antagonist naltrexone (50 mg, n=40) or placebo (n=40) to healthy humans and measured cue-induced responding with a Pavlovian-instrumental transfer task and reward impulsivity with a delay discounting task. Mood was assessed using a visual analogue scale. Compared with placebo, amisulpride significantly suppressed cue-induced responding and reward impulsivity. The effects of naltrexone were similar, although less pronounced. Both amisulpride and naltrexone decreased average mood ratings compared with placebo. Our results demonstrate that a selective blockade of dopamine D2/D3 receptors reduces cue-induced responding and reward impulsivity in healthy humans. Antagonizing μ-opioid receptors has similar effects for cue-induced responding and to a lesser extent for reward impulsivity.
authors.affiliation: Department of Economics, Laboratory for Social and Neural Systems Research, University of Zurich, Zurich, Switzerland.
authors.forename: S C
authors.initials: SC
authors.lastname: Weber
authors.affiliation: Institute of Anesthesiology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Beck-Schimmer
authors.affiliation: Institute of Anesthesiology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: M-E
authors.initials: ME
authors.lastname: Kajdi
authors.affiliation: Institute of Clinical Chemistry, University Hospital Zurich, Zurich, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Müller
authors.affiliation: Department of Economics, Laboratory for Social and Neural Systems Research, University of Zurich, Zurich, Switzerland.|Neuroscience Center Zurich, University of Zurich, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland.
authors.forename: P N
authors.initials: PN
authors.lastname: Tobler
authors.affiliation: Neuroscience Center Zurich, University of Zurich, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland.|Experimental and Clinical Pharmacopsychology, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland.
authors.forename: B B
authors.initials: BB
authors.lastname: Quednow
mesh_terms: D000077582:Amisulpride; D003463:Cues; D065786:Delay Discounting / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007175:Impulsive Behavior / Q000187:drug effects*; D008297:Male; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors; D012201:Reward; D013469:Sulpiride / Q000031:analogs & derivatives* / Q000494:pharmacology; D055815:Young Adult
chemical_list: C581293:DRD2 protein, human; C493593:DRD3 protein, human; D018492:Dopamine Antagonists; D009292:Narcotic Antagonists; C485764:OPRM1 protein, human; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D017450:Receptors, Opioid, mu; D009271:Naltrexone; D013469:Sulpiride; D000077582:Amisulpride