Acetylcholine and noradrenaline enhance foraging optimality in humans

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 120; no. 36; p. e2305596120
• Main Authors: Doren, Nick, Chung, Hui-Kuan, Grueschow, Marcus, Quednow, Boris B., Hayward-Könnecke, Helen, Jetter, Alexander, Tobler, Philippe N.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 05.09.2023
• Subjects: Acetylcholine; Acetylcholine receptors (nicotinic); Biological Sciences; Blindness; Cholinergics; Dopamine; Dopamine receptors; Double-Blind Method; Forage; Humans; Inhibitors; Mental disorders; Methylphenidate; Nicotine; Nicotine - pharmacology; Noradrenaline; Norepinephrine; Optimization; Placebos; Reboxetine; Temporal perception; exploration; value-based decision-making; marginal value theorem; cognitive enhancers; stay-or-switch
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.2305596120

Foraging theory prescribes when optimal foragers should leave the current option for more rewarding alternatives. Actual foragers often exploit options longer than prescribed by the theory, but it is unclear how this foraging suboptimality arises. We investigated whether the upregulation of cholinergic, noradrenergic, and dopaminergic systems increases foraging optimality. In a double-blind, between-subject design, participants (N = 160) received placebo, the nicotinic acetylcholine receptor agonist nicotine , a noradrenaline reuptake inhibitor reboxetine , or a preferential dopamine reuptake inhibitor methylphenidate , and played the role of a farmer who collected milk from patches with different yield. Across all groups, participants on average overharvested. While methylphenidate had no effects on this bias, nicotine, and to some extent also reboxetine, significantly reduced deviation from foraging optimality, which resulted in better performance compared to placebo. Concurring with amplified goal-directedness and excluding heuristic explanations, nicotine independently also improved trial initiation and time perception. Our findings elucidate the neurochemical basis of behavioral flexibility and decision optimality and open unique perspectives on psychiatric disorders affecting these functions.