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首页> 美国卫生研究院文献>PLoS Clinical Trials >A Genetic Polymorphism of the Endogenous Opioid Dynorphin Modulates Monetary Reward Anticipation in the Corticostriatal Loop
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A Genetic Polymorphism of the Endogenous Opioid Dynorphin Modulates Monetary Reward Anticipation in the Corticostriatal Loop

机译：内源性阿片类强啡肽的遗传多态性调节皮质口环中的货币奖励预期。

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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.
机译：强啡肽/κ阿片受体系统（KOP-R）已显示出在不同类型的行为调节中起作用，包括与奖励相关的行为和对药物的渴望。已经显示，强啡肽原（PDYN）基因的可变核苷酸串联重复序列（68 bp VNTR）功能多态性具有3个或4个重复序列（HH基因型）的等位基因与强啡肽的水平高于具有1个或2个等位基因的等位基因。重复（LL基因型）。我们对前筛查的N = 71名健康参与者进行了功能磁共振成像，以研究这种多态性对奖励预期期间边缘皮质皮质口环中脑激活的影响。预期可能会有金钱回报时，内侧眶额叶皮层（mOFC）中具有HH基因型的个体显示出比具有LL基因型的个体更高的激活。此外，HH基因型在奖励预期期间显示出mOFC与VMPFC，亚属前扣带回皮层和腹侧纹状体之间更强的功能耦合（通过有效的连通性分析评估）。这暗示着具有HH基因型的个体对即将获得的奖励的敏感性更高，从而导致获得这些奖励的动机更高。这些发现为人类提供了第一个证据，即PDYN多态性可调节与预期奖励有关的神经过程，这最终可能有助于解释成瘾和药物滥用之间的基因型差异。

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