Dopaminergic neurotransmission plays a pivotal role in appetitively motivated behavior in mammals, including humans. Notably, action and valence are not independent in motivated tasks, and it is particularly difficult for humans to learn the inhibition of an action to obtain a reward. We have previously observed that the carriers of the DRD2/ANKK1 TaqIA A1 allele, that has been associated with reduced striatal dopamine D2 receptor expression, showed a diminished learning performance when required to learn response inhibition to obtain rewards, a finding that was replicated in two independent cohorts. With our present study, we followed two aims: first, we aimed to replicate our finding on the DRD2/ANKK1 TaqIA polymorphism in a third independent cohort (N = 99) and to investigate the nature of the genetic effects more closely using trial-by-trial behavioral analysis and computational modeling in the combined dataset (N = 281). Second, we aimed to assess a potentially modulatory role of prefrontal dopamine availability, using the widely studied COMT Val108/158Met polymorphism as a proxy. We first report a replication of the above mentioned finding. Interestingly, after combining all three cohorts, exploratory analyses regarding the COMT Val108/158Met polymorphism suggest that homozygotes for the Met allele, which has been linked to higher prefrontal dopaminergic tone, show a lower learning bias. Our results corroborate the importance of genetic variability of the dopaminergic system in individual learning differences of action–valence interaction and, furthermore, suggest that motivational learning biases are differentially modulated by genetic determinants of striatal and prefrontal dopamine function.

多巴胺能神经传递在包括人类在内的哺乳动物的食欲动机行为中起关键作用。值得注意的是，在有动机的任务中，动作和效价并不是独立的，人类特别难以学习抑制动作以获得奖励。我们之前观察到，与纹状体多巴胺 D2 受体表达减少相关的 DRD2/ANKK1 TaqIA A1 等位基因的携带者在需要学习反应抑制以获得奖励时表现出学习能力下降，这一发现在两个独立的队列。在我们目前的研究中，我们遵循两个目标：首先，我们旨在在第三个独立队列中复制我们对 DRD2/ANKK1 TaqIA 多态性的发现（N = 99），并使用组合数据集中的逐次试验行为分析和计算建模更密切地研究遗传效应的性质（N = 281)。其次，我们旨在评估前额叶多巴胺可用性的潜在调节作用，使用广泛研究的 COMT Val108/158Met 多态性作为代理。我们首先报告上述发现的复制。有趣的是，在结合所有三个队列后，关于 COMT Val108/158Met 多态性的探索性分析表明，与较高的前额叶多巴胺能张力相关的 Met 等位基因的纯合子显示出较低的学习偏差。我们的结果证实了多巴胺能系统的遗传变异在个体学习行为-价相互作用的差异中的重要性，此外，表明动机学习偏差受到纹状体和前额叶多巴胺功能的遗传决定因素的不同调节。