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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Gene-gene interaction associated with neural reward sensitivity
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Gene-gene interaction associated with neural reward sensitivity

机译：基因-基因相互作用与神经奖励敏感性相关

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Reward processing depends on dopaminergic neurotransmission and is modulated by factors affecting dopamine (DA) reuptake and degradation. We used fMRI and a guessing task sensitive to reward-related activation in the prefrontal cortex and ventral striatum to study how individual variation in genes contributing to DA reuptake [DA transporter (DAT)] and degradation [catechol-o-methyltransferase (COMT)] influences reward processing. Prefrontal activity, evoked by anticipation of reward irrespective of reward probability and magnitude, was COMT genotype-dependent. Volunteers homozygous for the Met allele, associated with lower enzyme activity and presumably greater DA availability, showed larger responses compared with volunteers homozygous for the Val allele. A similar COMT effect was observed in the ventral striatum. As reported previously, the ventral striatum was also found to code gain-related expected value, i.e., the product of reward magnitude and gain probability. Individual differences in ventral striatal sensitivity for value were in part explained by an epistatic gene-gene interaction between COMT and DAT. Although most genotype combinations exhibited the expected activity increase with more likely and larger rewards, two genotype combinations (COMT Met/Met DAT 10R and COMT Val/Val 9R) were associated with blunted ventral striatal responses. In view of a consistent relationship between reduced reward sensitivity and addiction, our findings point to a potential genetic basis for vulnerability to addiction.
机译：奖励过程取决于多巴胺能神经传递，并受影响多巴胺（DA）再摄取和降解的因素调节。我们使用功能磁共振成像和对额叶前额叶和腹侧纹状体中奖励相关激活敏感的猜测任务，研究了基因的个体差异如何导致DA再摄取[DA转运蛋白（DAT）]和降解[儿茶酚-O-甲基转移酶（COMT）]影响奖励处理。前额活动是由奖励的预期引起的，而与奖励的可能性和幅度无关，是COMT基因型依赖性的。与Val等位基因纯合子的志愿者相比，Met等位基因纯合子的志愿者具有较低的酶活性和大概更高的DA利用率，显示出更大的反应。在腹侧纹状体中观察到类似的COMT作用。如先前所报道的，还发现腹侧纹状体编码与增益有关的期望值，即，奖励幅度与增益概率的乘积。腹侧纹状体对值的敏感性的个体差异部分地由COMT和DAT之间的上位基因-基因相互作用来解释。尽管大多数基因型组合表现出预期的活动性增加，并具有更大的可能性和更大的回报，但两种基因型组合（COMT Met / Met DAT 10R和COMT Val / Val 9R）与腹侧纹状体反应迟钝相关。鉴于降低的奖励敏感性和成瘾之间存在一致的关系，我们的研究结果指出了成瘾易感性的潜在遗传基础。

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