Davis, J. M., & Bailey, S. P. (1997). Possible mechanisms of central nervous system fatigue during exercise. Medicine and Science in Sports and Exercise, 29(1), 45-57.

"Fatigue of voluntary muscular effort is a complex phenomenon. To date, relatively little attention has been placed on the role of the central nervous system (CNS) in fatigue during exercise despite the fact that the unwillingness to generate and maintain adequate CNS drive to the working muscle is the most likely explanation of fatigue for most people during normal activities. Several biological mechanisms have been proposed to explain CNS fatigue. Hypotheses have been developed for several neurotransmitters including serotonin (5-HT; 5-hydroxytryptamine), dopamine, and acetylcholine. The most prominent one involves an increase in 5-HT activity in various brain regions. Good evidence suggests that increases and decreases in brain 5-HT activity during prolonged exercise hasten and delay fatigue, respectively, and nutritional manipulations designed to attenuate brain 5-HT synthesis during prolonged exercise improve endurance performance. Other neuromodulators that may influence fatigue during exercise include cytokines and ammonia. Increases in several cytokines have been associated with reduced exercise tolerance associated with acute viral or bacterial infection. Accumulation of ammonia in the blood and brain during exercise could also negatively effect the CNS function and fatigue. Clearly fatigue during prolonged exercise is influenced by multiple CNS and peripheral factors. Further elucidation of how CNS influences affect fatigue is relevant for achieving optimal muscular performance in athletics as well as everyday life."

Implication. Fatigue in sporting exercise is a complex phenomenon. Various aspects have been hypothesized as well as measured. Unfortunately, coaches have normally focused on one form of fatigue in one aspect of physiology and devised training programs to improve performance in that domain. That is an unsatisfactory and unjustified coaching manner. It is likely that the fatigue of extended and frequent exhausting training bouts will mimic or very adequately prepare an athlete for a short-term performance. Only when practice activities simulate the stimulation received in competitive settings and require the skill and psychological elements expected in those settings will training produce efficient improvements in performances that are relevant to competitions.

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