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

Open Access
Authors
  • Andrew Westbrook
  • Ruben van den Bosch
  • Lieke Hofmans ORCID logo
  • Danae Papadopetraki
  • Jessica I. Määttä
  • Anne G.E. Collins
  • Michael J. Frank
  • Roshan Cools
Publication date 09-07-2025
Journal Nature Communications
Article number 6320
Volume | Issue number 16 | 1
Number of pages 13
Organisations
  • Faculty of Social and Behavioural Sciences (FMG) - Psychology Research Institute (PsyRes)
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).
Document type Article
Language English
Published at https://doi.org/10.1038/s41467-025-61099-0
Other links https://www.scopus.com/pages/publications/105010656968
Downloads
Supplementary materials
Permalink to this page
Back