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Central Fatigue

The Serotonin Hypothesis and Beyond

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Abstract

The original central fatigue hypothesis suggested that an exercise-induced increase in extracellular serotonin concentrations in several brain regions contributed to the development of fatigue during prolonged exercise. Serotonin has been linked to fatigue because of its well known effects on sleep, lethargy and drowsiness and loss of motivation. Several nutritional and pharmacological studies have attempted to manipulate central serotonergic activity during exercise, but this work has yet to provide robust evidence for a significant role of serotonin in the fatigue process. However, it is important to note that brain function is not determined by a single neurotransmitter system and the interaction between brain serotonin and dopamine during prolonged exercise has also been explored as having a regulative role in the development of fatigue. This revised central fatigue hypothesis suggests that an increase in central ratio of serotonin to dopamine is associated with feelings of tiredness and lethargy, accelerating the onset of fatigue, whereas a low ratio favours improved performance through the maintenance of motivation and arousal. Convincing evidence for a role of dopamine in the development of fatigue comes from work investigating the physiological responses to amphetamine use, but other strategies to manipulate central catecholamines have yet to influence exercise capacity during exercise in temperate conditions. Recent findings have, however, provided support for a significant role of dopamine and noradrenaline (norepinephrine) in performance during exercise in the heat. As serotonergic and catecholaminergic projections innervate areas of the hypothalamus, the thermoregulatory centre, a change in the activity of these neurons may be expected to contribute to the control of body temperature whilst at rest and during exercise. Fatigue during prolonged exercise clearly is influenced by a complex interaction between peripheral and central factors.

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Acknowledgements

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

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Authors and Affiliations

  1. Department Human Physiology and Sportsmedicine, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium

    Romain Meeusen, Hiroshi Hasegawa, Bart Roelands & Maria F. Piacentini

  2. School of Sport and Exercise Sciences, Loughborough University, Leicestershire, UK

    Philip Watson

  3. Laboratory of Exercise Physiology, Faculty of Integrated Arts and Sciences, Hiroshima University, Higashihiroshima, Japan

    Hiroshi Hasegawa

  4. Department of Human Movement and Sport Sciences, Istituto Universitario di Scienze Motorie, Rome, Italy

    Maria F. Piacentini

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  1. Romain Meeusen
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Correspondence to Romain Meeusen.

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Meeusen, R., Watson, P., Hasegawa, H. et al. Central Fatigue. Sports Med 36, 881–909 (2006). https://doi.org/10.2165/00007256-200636100-00006

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