title: Opioid Modulation of Value-Based Decision-Making in Healthy Humans.
abstract: Modifying behavior to maximize reward is integral to adaptive decision-making. In rodents, the μ-opioid receptor (MOR) system encodes motivation and preference for high-value rewards. Yet it remains unclear whether and how human MORs contribute to value-based decision-making. We reasoned that if the human MOR system modulates value-based choice, this would be reflected by opposite effects of agonist and antagonist drugs. In a double-blind pharmacological cross-over study, 30 healthy men received morphine (10 mg), placebo, and the opioid antagonist naltrexone (50 mg). They completed a two-alternative decision-making task known to induce a considerable bias towards the most frequently rewarded response option. To quantify MOR involvement in this bias, we fitted accuracy and reaction time data with the drift-diffusion model (DDM) of decision-making. The DDM analysis revealed the expected bidirectional drug effects for two decision subprocesses. MOR stimulation with morphine increased the preference for the stimulus with high-reward probability (shift in starting point). Compared to placebo, morphine also increased, and naltrexone reduced, the efficiency of evidence accumulation. Since neither drug affected motor-coordination, speed-accuracy trade-off, or subjective state (indeed participants were still blinded after the third session), we interpret the MOR effects on evidence accumulation efficiency as a consequence of changes in effort exerted in the task. Together, these findings support a role for the human MOR system in value-based choice by tuning decision-making towards high-value rewards across stimulus domains.
authors.affiliation: The Department of Psychology, University of Oslo, Oslo, Norway.|Norwegian Center for Addiction Research, Department of Clinical Medicine, University of Oslo, Oslo, Norway.|Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors.forename: Marie
authors.initials: M
authors.lastname: Eikemo
authors.affiliation: The Department of Psychology, University of Oslo, Oslo, Norway.|Department of Child Health, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Guido
authors.initials: G
authors.lastname: Biele
authors.affiliation: The Department of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Frode
authors.initials: F
authors.lastname: Willoch
authors.affiliation: The Department of Psychology, University of Oslo, Oslo, Norway.
authors.forename: Lotte
authors.initials: L
authors.lastname: Thomsen
authors.affiliation: The Department of Psychology, University of Oslo, Oslo, Norway.|The Intervention Centre, Oslo University Hospital, Oslo, Norway.
authors.forename: Siri
authors.initials: S
authors.lastname: Leknes
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000494:pharmacology*; D003198:Computer Simulation; D018592:Cross-Over Studies; D003657:Decision Making / Q000187:drug effects* / Q000502:physiology; D004311:Double-Blind Method; D006801:Humans; D008959:Models, Neurological; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000378:metabolism; D012201:Reward; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D009271:Naltrexone; D009020:Morphine