DAT1 Polymorphism Determines L-DOPA Effects on Learning about Others’ Prosociality

Despite that a wealth of evidence links striatal dopamine to individualś reward learning performance in non-social environments, the neurochemical underpinnings of such learning during social interaction are unknown. Here, we show that the administration of 300 mg of the dopamine precursor L-DOPA to 200 healthy male subjects influences learning about a partners’ prosocial preferences in a novel social interaction task, which is akin to a repeated trust game. We found learning to be modulated by a well-established genetic marker of striatal dopamine levels, the 40-bp variable number tandem repeats polymorphism of the dopamine transporter (DAT1 polymorphism). In particular, we found that L-DOPA improves learning in 10/10R genoype subjects, who are assumed to have lower endogenous striatal dopamine levels and impairs learning in 9/10R genotype subjects, who are assumed to have higher endogenous dopamine levels. These findings provide first evidence for a critical role of dopamine in learning whether an interaction partner has a prosocial or a selfish personality. The applied pharmacogenetic approach may open doors to new ways of studying psychiatric disorders such as psychosis, which is characterized by distorted perceptions of others’ prosocial attitudes.尽管已有大量研究证据表明，纹状体多巴胺（striatal dopamine）与个体在非社交环境中的奖赏学习表现存在显著关联，但社交互动场景下此类学习的神经化学基础仍未被阐明。 本研究招募200名健康男性受试者，给予300mg多巴胺前体左旋多巴（L-DOPA），结果发现该药物会影响受试者在一项类似于重复版信任博弈的新型社交互动任务中，对合作伙伴亲社会偏好的学习过程。 我们观察到，学习表现受到一项公认的纹状体多巴胺水平遗传标记的调控：即多巴胺转运体（dopamine transporter, DAT1）的40bp可变数目串联重复序列多态性。 具体而言，左旋多巴可改善10/10R基因型受试者的学习能力——这类人群被认为内源性纹状体多巴胺水平较低；同时会损害9/10R基因型受试者的学习能力，这类人群被认为内源性纹状体多巴胺水平较高。 本研究首次为多巴胺在个体学习判断互动伙伴具有亲社会或自私人格的过程中发挥关键作用提供了实验证据。 本研究采用的药物遗传学研究范式，或为以对他人亲社会态度的感知扭曲为特征的精神病性障碍等精神疾病的研究开辟新的路径。