Dopamine and acetylcholine have distinct roles in delay- and effort-based decision-making in humans

• Published in: PLoS biology Vol. 22; no. 7; p. e3002714
• Main Authors: Erfanian Abdoust, Mani, Froböse, Monja Isabel, Schnitzler, Alfons, Schreivogel, Elisabeth, Jocham, Gerhard
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.07.2024
• Subjects: Acetylcholine; Acetylcholine - metabolism; Adult; Biology and Life Sciences; Decision Making - drug effects; Decision Making - physiology; Decision-making; Delay Discounting - drug effects; Delay Discounting - physiology; Dopamine; Dopamine - metabolism; Female; Haloperidol - pharmacology; Humans; Male; Medicine and Health Sciences; Physical Sciences; Physiological aspects; Psychological aspects; Receptor, Muscarinic M1 - metabolism; Receptors, Dopamine D2 - metabolism; Reward; Social Sciences; Young Adult; Germany
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.3002714

In everyday life, we encounter situations that require tradeoffs between potential rewards and associated costs, such as time and (physical) effort. The literature indicates a prominent role for dopamine in discounting of both delay and effort, with mixed findings for delay discounting in humans. Moreover, the reciprocal antagonistic interaction between dopaminergic and cholinergic transmission in the striatum suggests a potential opponent role of acetylcholine in these processes. We found opposing effects of dopamine D2 (haloperidol) and acetylcholine M1 receptor (biperiden) antagonism on specific components of effort-based decision-making in healthy humans: haloperidol decreased, whereas biperiden increased the willingness to exert physical effort. In contrast, delay discounting was reduced under haloperidol, but not affected by biperiden. Together, our data suggest that dopamine, acting at D2 receptors, modulates both effort and delay discounting, while acetylcholine, acting at M1 receptors, appears to exert a more specific influence on effort discounting only.