Distinct roles of dopamine and noradrenaline in physical fatigue

Abstract

This triple‐blinded randomized crossover study investigated the roles of dopamine (DA) and noradrenaline (NA) in regulatingexercise performance and fatigue using acute pharmacological manipulation. Eighteen healthy adults (9 males and 9 females;mean age = 23.4 ± 2.2 years) completed three experimental conditions. Participants ingested methylphenidate (MPH; 20 mg;primarily enhancing DA signaling), reboxetine (REB; 8 mg; selectively enhancing NA signaling), or placebo (10 mg lactose) prior toperforming dynamic leg extensions until exhaustion. Behavioral, subjective, and physiological responses were assessed to evaluatedrug‐specific effects using (generalized) linear mixed‐effects models. The fatiguing task effectively induced exhaustion in allconditions, evidenced by increases in self‐reported fatigue and exertion, heart rate, and blood lactate levels. MPH did not signif-icantly improve the number of leg extension repetitions (+3.1%, p = 0.23) or perceived exertion ratings. Perceived performance andvigor increased, while sleepiness decreased across pretask and posttask assessments. Posttask temporal demand and overall taskload were also reduced. In contrast, REB significantly reduced the number of leg extension repetitions (−13.2%, p < 0.001) withoutaltering perceived exertion, mood, or performance perception. These findings show that DA and NA systems differently affectfatigue regulation. DA mainly influences cognitive and perceptual aspects, improving alertness and mood without significantlyenhancing physical performance. In contrast, NA reduced physical performance without altering fatigue perception, indicating adissociation between subjective fatigue and actual capacity. This study provides new evidence on how DA and NA shape bothperformance and perception during fatiguing leg‐extension exercise in males and females.