Methamphetamine-induced adaptation of learning rate dynamics depend on baseline performance

• Published in: eLife Vol. 13
• Main Authors: Kirschner, Hans, Molla, Hanna M, Nassar, Matthew R, de Wit, Harriet, Ullsperger, Markus
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 21.07.2025; eLife Sciences Publications, Ltd
• Subjects: Adult; Blindness; Catecholamines; Central Nervous System Stimulants - administration & dosage; Central Nervous System Stimulants - pharmacology; computational neuroscience; Dopamine; Double-Blind Method; Drugs; Female; Flexibility; Humans; learning; Learning - drug effects; Male; Methamphetamine; Methamphetamine - administration & dosage; Methamphetamine - pharmacology; Neuroscience; Reversal learning; Reversal Learning - drug effects; Young Adult; catecholamines; learning; computational neuroscience; human; neuroscience
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.101413

The ability to calibrate learning according to new information is a fundamental component of an organism’s ability to adapt to changing conditions. Yet, the exact neural mechanisms guiding dynamic learning rate adjustments remain unclear. Catecholamines appear to play a critical role in adjusting the degree to which we use new information over time, but individuals vary widely in the manner in which they adjust to changes. Here, we studied the effects of a low dose of methamphetamine (MA), and individual differences in these effects, on probabilistic reversal learning dynamics in a within-subject, double-blind, randomized design. Participants first completed a reversal learning task during a drug-free baseline session to provide a measure of baseline performance. Then they completed the task during two sessions, one with MA (20 mg oral) and one with placebo (PL). First, we showed that, relative to PL, MA modulates the ability to dynamically adjust learning from prediction errors. Second, this effect was more pronounced in participants who performed moderately low at baseline. These results present novel evidence for the involvement of catecholaminergic transmission on learning flexibility and highlights that baseline performance modulates the effect of the drug.