Striatal dopamine can enhance both fast working memory, and slow reinforcement learning, while reducing implicit effort cost sensitivity

Andrew Westbrook (), Ruben van den Bosch, Lieke Hofmans, Danae Papadopetraki, Jessica I. Määttä, Anne G. E. Collins, Michael J. Frank and Roshan Cools
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Andrew Westbrook: Rutgers University
Ruben van den Bosch: Radboud University
Lieke Hofmans: University of Amsterdam
Danae Papadopetraki: Radboud University
Jessica I. Määttä: Stockholm University
Anne G. E. Collins: University of California at Berkeley
Michael J. Frank: Brown University
Roshan Cools: Radboud University

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract Associations can be learned incrementally, via reinforcement learning (RL), or stored instantly in working memory (WM). While WM is fast, it is also capacity-limited and effortful. Striatal dopamine may promote WM, by facilitating WM updating and effort exertion and also RL, by boosting plasticity. Yet, prior studies have failed to distinguish between the effects of dopamine manipulations on RL versus WM. N = 100 participants completed a paradigm isolating these systems in a double-blind study measuring dopamine synthesis with [18F]-FDOPA PET imaging and manipulating dopamine with methylphenidate and sulpiride. We find that learning is enhanced among high synthesis capacity individuals and by methylphenidate, but impaired by sulpiride. Methylphenidate also blunts implicit effort cost learning. Computational modeling reveals that individuals with higher dopamine synthesis capacity rely more on WM, while methylphenidate boosts their RL rates. The D2 receptor antagonist sulpiride reduces accuracy due to diminished WM involvement and faster WM decay. We conclude that dopamine enhances both slow RL, and fast WM, by promoting plasticity and reducing implicit effort sensitivity. This work was completed as part of a registered trial with the Overview of Medical Research in the Netherlands (NL-OMON43196).

Date: 2025
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DOI: 10.1038/s41467-025-61099-0

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