title: A genetic polymorphism of the endogenous opioid dynorphin modulates monetary reward anticipation in the corticostriatal loop.
abstract: The dynorphin/κ-opioid receptor (KOP-R) system has been shown to play a role in different types of behavior regulation, including reward-related behavior and drug craving. It has been shown that alleles with 3 or 4 repeats (HH genotype) of the variable nucleotide tandem repeat (68-bp VNTR) functional polymorphism of the prodynorphin (PDYN) gene are associated with higher levels of dynorphin peptides than alleles with 1 or 2 repeats (LL genotype). We used fMRI on N = 71 prescreened healthy participants to investigate the effect of this polymorphism on cerebral activation in the limbic-corticostriatal loop during reward anticipation. Individuals with the HH genotype showed higher activation than those with the LL genotype in the medial orbitofrontal cortex (mOFC) when anticipating a possible monetary reward. In addition, the HH genotype showed stronger functional coupling (as assessed by effective connectivity analyses) of mOFC with VMPFC, subgenual anterior cingulate cortex, and ventral striatum during reward anticipation. This hints at a larger sensitivity for upcoming rewards in individuals with the HH genotype, resulting in a higher motivation to attain these rewards. These findings provide first evidence in humans that the PDYN polymorphism modulates neural processes associated with the anticipation of rewards, which ultimately may help to explain differences between genotypes with respect to addiction and drug abuse.
authors.affiliation: Social, Cognitive and Affective Neuroscience Unit, Department of Basic Psychological Research and Research Methods, Faculty of Psychology, University of Vienna, Vienna, Austria.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Votinov
authors.affiliation: Social, Cognitive and Affective Neuroscience Unit, Department of Basic Psychological Research and Research Methods, Faculty of Psychology, University of Vienna, Vienna, Austria.
authors.forename: Juergen
authors.initials: J
authors.lastname: Pripfl
authors.affiliation: MR Center of Excellence, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Windischberger
authors.affiliation: MR Center of Excellence, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.
authors.forename: Klaudius
authors.initials: K
authors.lastname: Kalcher
authors.affiliation: Department of Neurology, Medical University of Vienna, Vienna, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Zimprich
authors.affiliation: Department of Neurology, Medical University of Vienna, Vienna, Austria.
authors.forename: Fritz
authors.initials: F
authors.lastname: Zimprich
authors.affiliation: MR Center of Excellence, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.
authors.forename: Ewald
authors.initials: E
authors.lastname: Moser
authors.affiliation: Social, Cognitive and Affective Neuroscience Unit, Department of Basic Psychological Research and Research Methods, Faculty of Psychology, University of Vienna, Vienna, Austria.
authors.forename: Claus
authors.initials: C
authors.lastname: Lamm
authors.affiliation: Social, Cognitive and Affective Neuroscience Unit, Department of Basic Psychological Research and Research Methods, Faculty of Psychology, University of Vienna, Vienna, Austria ; Department of Psychology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Uta
authors.initials: U
authors.lastname: Sailer
mesh_terms: D059031:Anticipation, Psychological / Q000502:physiology*; D003342:Corpus Striatum / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D004399:Dynorphins / Q000235:genetics*; D005838:Genotype; D006801:Humans; D065726:Limbic Lobe / Q000502:physiology*; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D018598:Minisatellite Repeats; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012201:Reward
chemical_list: D017931:DNA Primers; D004399:Dynorphins