Dopamine and Norepinephrine Differentially Mediate the Exploration-exploitation Tradeoff.

Abstract

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 co-activated 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.Significance Statement Both dopamine (DA) and norepinephrine (NE) have been implicated in the decision making process. Although these two catecholamines have shared aspects of their biosynthetic pathways and projection targets, they are thought to exert many core functions via distinct neural targets and receptor subtypes. However, the computational neuroscience literature often ascribes similar roles to these catecholamines, despite the above evidence. Resolving this discrepancy is important in guiding mechanistic hypotheses emerging from computational psychiatric approaches. This study examines the role of dopamine and norepinephrine on the explore-exploit tradeoff. By testing mice, we were able to compare multiple pharmacological agents within subjects, and examine sources of individual differences, allowing direct comparison between the effects of these two catecholamines in modulating decision making.