Votinov Mikhail, Pripfl Juergen, Windischberger Christian, Kalcher Klaudius, Zimprich Alexander, Zimprich Fritz, Moser Ewald, Lamm Claus, Sailer Uta
Social, Cognitive and Affective Neuroscience Unit, Department of Basic Psychological Research and Research Methods, Faculty of Psychology, University of Vienna, Vienna, Austria.
MR Center of Excellence, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.
PLoS One. 2014 Feb 25;9(2):e89954. doi: 10.1371/journal.pone.0089954. eCollection 2014.
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.
强啡肽/κ-阿片受体（KOP-R）系统已被证明在不同类型的行为调节中发挥作用，包括与奖赏相关的行为和药物渴望。研究表明，前强啡肽（PDYN）基因可变核苷酸串联重复序列（68bp VNTR）功能多态性中具有3个或4个重复序列的等位基因（HH基因型），比具有1个或2个重复序列的等位基因（LL基因型）与更高水平的强啡肽相关。我们对71名预先筛选的健康参与者进行了功能磁共振成像（fMRI），以研究这种多态性在奖赏预期期间对边缘-皮质-纹状体环路中大脑激活的影响。在预期可能的金钱奖励时，HH基因型个体在内侧眶额皮质（mOFC）中的激活高于LL基因型个体。此外，在奖赏预期期间，HH基因型显示出mOFC与腹内侧前额叶皮质（VMPFC）、膝下前扣带回皮质和腹侧纹状体之间更强的功能耦合（通过有效连接分析评估）。这暗示HH基因型个体对即将到来的奖励具有更大的敏感性，从而产生更高的获得这些奖励的动机。这些发现首次在人类中证明，PDYN多态性调节与奖赏预期相关的神经过程，这最终可能有助于解释不同基因型在成瘾和药物滥用方面的差异。
