A genetic polymorphism of the endogenous opioid dynorphin modulates monetary reward anticipation in the corticostriatal loop.

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) functiona...

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Main Authors: Mikhail Votinov, Juergen Pripfl, Christian Windischberger, Klaudius Kalcher, Alexander Zimprich, Fritz Zimprich, Ewald Moser, Claus Lamm, Uta Sailer
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0089954&type=printable
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author Mikhail Votinov
Mikhail Votinov
Juergen Pripfl
Christian Windischberger
Klaudius Kalcher
Alexander Zimprich
Fritz Zimprich
Ewald Moser
Claus Lamm
Uta Sailer
author_facet Mikhail Votinov
Mikhail Votinov
Juergen Pripfl
Christian Windischberger
Klaudius Kalcher
Alexander Zimprich
Fritz Zimprich
Ewald Moser
Claus Lamm
Uta Sailer
author_sort Mikhail Votinov
collection DOAJ
description 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.
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spelling doaj-art-8b6cf6a1798745d1bf60a3bbc11840a72025-08-20T02:15:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0192e8995410.1371/journal.pone.0089954A genetic polymorphism of the endogenous opioid dynorphin modulates monetary reward anticipation in the corticostriatal loop.Mikhail VotinovMikhail VotinovJuergen PripflChristian WindischbergerKlaudius KalcherAlexander ZimprichFritz ZimprichEwald MoserClaus LammUta SailerThe 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0089954&type=printable
spellingShingle Mikhail Votinov
Mikhail Votinov
Juergen Pripfl
Christian Windischberger
Klaudius Kalcher
Alexander Zimprich
Fritz Zimprich
Ewald Moser
Claus Lamm
Uta Sailer
A genetic polymorphism of the endogenous opioid dynorphin modulates monetary reward anticipation in the corticostriatal loop.
PLoS ONE
title A genetic polymorphism of the endogenous opioid dynorphin modulates monetary reward anticipation in the corticostriatal loop.
title_full A genetic polymorphism of the endogenous opioid dynorphin modulates monetary reward anticipation in the corticostriatal loop.
title_fullStr A genetic polymorphism of the endogenous opioid dynorphin modulates monetary reward anticipation in the corticostriatal loop.
title_full_unstemmed A genetic polymorphism of the endogenous opioid dynorphin modulates monetary reward anticipation in the corticostriatal loop.
title_short A genetic polymorphism of the endogenous opioid dynorphin modulates monetary reward anticipation in the corticostriatal loop.
title_sort genetic polymorphism of the endogenous opioid dynorphin modulates monetary reward anticipation in the corticostriatal loop
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0089954&type=printable
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