Single Dose of a Dopamine Agonist Impairs Reinforcement Learning in Humans: Evidence From Event-Related Potentials and Computational Modeling of Striatal-Cortical Function

Animal findings have highlighted the modulatory role of phasic dopamine (DA) signaling in incentive learning, particularly in the acquisition of reward-related behavior. In humans, these processes remain largely unknown. In a recent study, we demonstrated that a single low dose of a D2/D3 agonist (pramipexole)-assumed to activate DA autoreceptors and thus reduce phasic DA bursts-impaired reward learning in healthy subjects performing a probabilistic reward task. The purpose of this study was to extend these behavioral findings using event-related potentials and computational modeling. Compared with the placebo group, participants receiving pramipexole showed increased feedback-related negativity to probabilistic rewards and decreased activation in dorsal anterior cingulate regions previously implicated in integrating reinforcement history over time. Additionally, findings of blunted reward learning in participants receiving pramipexole were simulated by reduced presynaptic DA signaling in response to reward in a neural network model of striatal-cortical function. These preliminary findings offer important insights on the role of phasic DA signals on reinforcement learning in humans and provide initial evidence regarding the spatiotemporal dynamics of brain mechanisms underlying these processes. Hum Brain Mapp 30:1963-1976, 2009. (C) 2008 Wiley-Liss, Inc.