# Distinct Roles of Dopamine and Noradrenaline in Physical Fatigue

## TL;DR

This study shows that dopamine and noradrenaline have different effects on physical fatigue and performance during exercise.

## Contribution

The study reveals distinct roles of dopamine and noradrenaline in separating cognitive-perceptual and physical aspects of fatigue.

## Key findings

- Dopamine increases alertness and perceived performance without improving physical performance.
- Noradrenaline reduces physical performance without affecting fatigue perception.
- Dopamine and noradrenaline systems regulate different aspects of fatigue in males and females.

## Abstract

This triple‐blinded randomized crossover study investigated the roles of dopamine (DA) and noradrenaline (NA) in regulating exercise 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 to performing dynamic leg extensions until exhaustion. Behavioral, subjective, and physiological responses were assessed to evaluate drug‐specific effects using (generalized) linear mixed‐effects models. The fatiguing task effectively induced exhaustion in all conditions, evidenced by increases in self‐reported fatigue and exertion, heart rate, and blood lactate levels. MPH did not significantly improve the number of leg extension repetitions (+3.1%, p = 0.23) or perceived exertion ratings. Perceived performance and vigor increased, while sleepiness decreased across pretask and posttask assessments. Posttask temporal demand and overall task load were also reduced. In contrast, REB significantly reduced the number of leg extension repetitions (−13.2%, p < 0.001) without altering perceived exertion, mood, or performance perception. These findings show that DA and NA systems differently affect fatigue regulation. DA mainly influences cognitive and perceptual aspects, improving alertness and mood without significantly enhancing physical performance. In contrast, NA reduced physical performance without altering fatigue perception, indicating a dissociation between subjective fatigue and actual capacity. This study provides new evidence on how DA and NA shape both performance and perception during fatiguing leg‐extension exercise in males and females.

Trial Registration: G095422N and identifier NCT05880342

Elevated brain dopamine levels boost alertness, vigor, and perceived performance without significantly enhancing leg extension performance in males and females.Elevated brain noradrenaline levels reduce leg extension performance while leaving perceptual responses unchanged in males and females.Dopaminergic and noradrenergic systems play distinct roles in separating cognitive‐perceptual and physical aspects of fatigue.

Elevated brain dopamine levels boost alertness, vigor, and perceived performance without significantly enhancing leg extension performance in males and females.

Elevated brain noradrenaline levels reduce leg extension performance while leaving perceptual responses unchanged in males and females.

Dopaminergic and noradrenergic systems play distinct roles in separating cognitive‐perceptual and physical aspects of fatigue.