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 the present study was to extend these behavioral findings using event-related potentials and computational modeling. Compared to 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 spatio-temporal dynamics of brain mechanisms underlying these processes.In recent years, the role of dopamine (DA) in reinforcement learning has been strongly emphasized. In particular, electrophysiological studies in non-human primates have shown that midbrain DA neurons code reward-related prediction errors: unpredicted rewards elicit phasic increases in DA neurons as well as phasic DA release (positive-prediction error), whereas omission of a predicted reward elicits phasic DA decreases (negative-prediction error) [Fiorillo et al., 2003;Schultz, 2007]. These phasic DA responses have been assumed to reflect a teaching signal for regions implicated in reward-related learning, including the anterior cingulate cortex (ACC) and basal ganglia [Holroyd and Coles, 2002]. Accordingly, when a positive prediction error occurs, learning about the consequences of the behavior that led to reward takes place; when a negative prediction error occurs, behaviors that led to lack Please address all correspondence to: Diego A. Pizzagalli, Ph.D., Department of Psychology, Harvard University, 1220 William James Hall, 33 Kirkland Street, Cambridge, MA 02138, USA, Phone: +1-617-496-8896, Fax: +1-617-495-3728, dap@wjh.harvard.edu. Disclosure/Conflict of Interest Dr. Pizzagalli has received research support from GlaxoSmithKline and Merck & Co., Inc. for projects unrelated to the present study. Dr. Evins has received research grant support from Janssen Pharmaceutica, Sanofi-Aventis, Astra Zeneca; research materials from GSK and Pfizer, and honoraria from Primedia, Inc. Moreover, Dr. Evins is an investigator in a NIDA-funded collaborative study with GSK. Dr. Santesso, Dr. Frank, Ms. Cowman Schetter, and Mr. Bogdan report no competing interests. ([Bayer and Glimacher, 2005;Garris et al., 1999;Montague ...