Reward-predicting cues motivate goal-directed behavior, but in unstable environments humans must also be able to flexibly update cue-reward associations. While the capacity of reward cues to trigger motivation ('reactivity') as well as flexibility in cue-reward associations have been linked to the neurotransmitter dopamine in humans, the specific contribution of the dopamine D1 receptor family to these behaviors remained elusive. To fill this gap, we conducted a randomized, placebo-controlled, double-blind pharmacological study testing the impact of three different doses of a novel D1 agonist (relative to placebo) on reactivity to reward-predicting cues (Pavlovian-to-instrumental transfer) and flexibility of cue-outcome associations (reversal learning). We observed that the impact of the D1 agonist crucially depended on baseline working memory functioning, which has been identified as a proxy for baseline dopamine synthesis capacity. Specifically, increasing D1 receptor stimulation strengthened Pavlovian-to-instrumental transfer in individuals with high baseline working memory capacity. In contrast, higher doses of the D1 agonist improved reversal learning only in individuals with low baseline working memory functioning. Our findings suggest a crucial and baseline-dependent role of D1 receptor activation in controlling both cue reactivity and the flexibility of cue-reward associations.

中文翻译：

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D1受体的激活影响人的反应性和对有价值线索的灵活性。

奖励预测提示会激发目标导向的行为，但是在不稳定的环境中，人类还必须能够灵活地更新提示与奖励的关联。尽管奖励线索触发动机（“反应性”）的能力以及线索与报酬关联的灵活性已与人类的神经递质多巴胺相关联，但多巴胺D1受体家族对这些行为的具体贡献仍然难以捉摸。为了填补这一空白，我们进行了一项随机，安慰剂对照，双盲药理学研究，测试了三种不同剂量的新型D1激动剂（相对于安慰剂）对回报预测线索（巴甫洛夫斯到器械转移）反应性的影响。 ）和提示/结果关联的灵活性（逆向学习）。我们观察到，D1激动剂的影响主要取决于基线工作记忆功能，该功能已被确定为基线多巴胺合成能力的代表。具体而言，增加D1受体刺激可增强具有高基线工作记忆能力的个体中从Pavlovian到器械的转移。相反，仅在基线工作记忆功能低的个体中，较高剂量的D1激动剂可改善逆向学习。我们的发现表明，D1受体激活在控制提示反应性和提示-奖励关联的灵活性方面具有至关重要的且依赖基线的作用。D1受体刺激的增加增强了具有高基线工作记忆能力的个体中Pavlovian向器械的转移。相反，仅在基线工作记忆功能低的个体中，较高剂量的D1激动剂可改善逆向学习。我们的发现表明，D1受体激活在控制提示反应性和提示-奖励关联的灵活性方面具有至关重要的且依赖基线的作用。D1受体刺激的增加增强了具有高基线工作记忆能力的个体中Pavlovian向器械的转移。相反，仅在基线工作记忆功能低的个体中，较高剂量的D1激动剂可改善逆向学习。我们的发现表明，D1受体激活在控制提示反应性和提示-奖励关联的灵活性方面具有至关重要的且依赖基线的作用。