title: Functional polymorphism of the mu-opioid receptor gene (OPRM1) influences reinforcement learning in humans.
abstract: Previous reports on the functional effects (i.e., gain or loss of function), and phenotypic outcomes (e.g., changes in addiction vulnerability and stress response) of a commonly occurring functional single nucleotide polymorphism (SNP) of the mu-opioid receptor (OPRM1 A118G) have been inconsistent. Here we examine the effect of this polymorphism on implicit reward learning. We used a probabilistic signal detection task to determine whether this polymorphism impacts response bias to monetary reward in 63 healthy adult subjects: 51 AA homozygotes and 12 G allele carriers. OPRM1 AA homozygotes exhibited typical responding to the rewarded response--that is, their bias to the rewarded stimulus increased over time. However, OPRM1 G allele carriers exhibited a decline in response to the rewarded stimulus compared to the AA homozygotes. These results extend previous reports on the heritability of performance on this task by implicating a specific polymorphism. Through comparison with other studies using this task, we suggest a possible mechanism by which the OPRM1 polymorphism may confer reduced response to natural reward through a dopamine-mediated decrease during positive reinforcement learning.
authors.affiliation: National Institute on Drug Abuse, Intramural Research Program, Baltimore, Maryland, United States of America. leemary@mail.nih.gov
authors.forename: Mary R
authors.initials: MR
authors.lastname: Lee
authors.forename: Courtney L
authors.initials: CL
authors.lastname: Gallen
authors.forename: Xiaochu
authors.initials: X
authors.lastname: Zhang
authors.forename: Colin A
authors.initials: CA
authors.lastname: Hodgkinson
authors.forename: David
authors.initials: D
authors.lastname: Goldman
authors.forename: Elliot A
authors.initials: EA
authors.lastname: Stein
authors.forename: Christina S
authors.initials: CS
authors.lastname: Barr
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D055030:Drug Users / Q000706:statistics & numerical data; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D017450:Receptors, Opioid, mu / Q000235:genetics*; D012054:Reinforcement, Psychology; D012201:Reward
chemical_list: C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu