Dopamine (DA) and norepinephrine (NE) have been repeatedly implicated in neuropsychiatric vulnerability, in part via their roles in mediating the decision-making processes. Although two neuromodulators share a synthesis pathway and are coactivated under states of arousal, they engage in distinct circuits and modulatory roles. However, the specific role of each neuromodulator in decision-making, in particular the exploration–exploitation tradeoff, remains unclear. Revealing how each neuromodulator contributes to exploration–exploitation tradeoff is important in guiding mechanistic hypotheses emerging from computational psychiatric approaches. To understand the differences and overlaps of the roles of these two catecholamine systems in regulating exploration, a direct comparison using the same dynamic decision-making task is needed. Here, we ran male and female mice in a restless two-armed bandit task, which encourages both exploration and exploitation. We systemically administered a nonselective DA antagonist (flupenthixol), a nonselective DA agonist (apomorphine), a NE beta-receptor antagonist (propranolol), and a NE beta-receptor agonist (isoproterenol) and examined changes in exploration within subjects across sessions. We found a bidirectional modulatory effect of dopamine on exploration. Increasing dopamine activity decreased exploration and decreasing dopamine activity increased exploration. The modulatory effect of beta-noradrenergic receptor activity on exploration was mediated by sex. Reinforcement learning model parameters suggested that dopamine modulation affected exploration via decision noise and norepinephrine modulation affected exploration via sensitivity to outcome. Together, these findings suggested that the mechanisms that govern the exploration–exploitation transition are sensitive to changes in both catecholamine functions and revealed differential roles for NE and DA in mediating exploration.

多巴胺 （DA） 和去甲肾上腺素 （NE） 一再与神经精神脆弱性有关，部分原因是它们在介导决策过程中的作用。尽管两种神经调节剂共享一个合成途径并在唤醒状态下被共激活，但它们参与不同的回路和调节作用。然而，每种神经调节剂在决策中的具体作用，特别是探索-利用权衡，仍不清楚。揭示每种神经调节剂如何促进探索-开发权衡，对于指导计算精神病学方法中出现的机制假设非常重要。为了了解这两种儿茶酚胺系统在调控勘探中的作用的差异和重叠，需要使用相同的动态决策任务进行直接比较。在这里，我们让雄性和雌性老鼠执行一项不安分的双臂强盗任务，这鼓励了探索和开发。我们系统地给予了非选择性 DA 拮抗剂 （氟喷噻醇）、非选择性 DA 激动剂 （阿扑吗啡）、NE β 受体拮抗剂 （普萘洛尔） 和 NE β 受体激动剂 （异丙肾上腺素），并检查了受试者在不同疗程中探查的变化。我们发现多巴胺对探索的双向调节作用。增加多巴胺活性减少探查，降低多巴胺活性增加探查。β-去甲肾上腺素能受体活性对探查的调节作用是由性别介导的。强化学习模型参数表明，多巴胺调制通过决策噪声影响探索，去甲肾上腺素调节通过对结果的敏感性影响探索。 总之，这些发现表明，控制勘探-开采过渡的机制对儿茶酚胺功能的变化很敏感，并揭示了 NE 和 DA 在介导勘探中的不同作用。