Sports Med 2006; 36 (10): 881-909

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 881 1. Fatigue: the Central Fatigue Hypothesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 882 2. Central Fatigue and Serotonin: the Evidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 885 2.1 Nutritional Manipulation of Neurotransmission: Branched-Chain Amino Acid, Tryptophan and Carbohydrate Supplementation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 889 2.2 Pharmacological Manipulation of Neurotransmission: Selective Serotonin Reuptake Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 891 2.3 Serotonin 5-HT Receptor Agonists or Antagonists . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 892 2.4 Combined Reuptake Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 893 2.5 Catecholaminergic Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 894 3. The Use of Prolactin and Other Hormones as Peripheral Indices of Brain Neurotransmitter Activity 896 4. Is ‘What We See What We Get’: is the Evidence for Central Fatigue that Straightforward? . . . . . . . 897 5. Are There Other Possible Factors Responsible for Central Fatigue? . . . . . . . . . . . . . . . . . . . . . . . . . . . . 898 6. Hyperthermia and Central Fatigue: Is There a Link with Brain Neurotransmitters? . . . . . . . . . . . . . . . . 900 6.1 Hyperthermia as a Possible Limiting Factor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 900 6.2 Is There a Link with Brain Neurotransmission? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 902 7. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 904 The original central fatigue hypothesis suggested that an exercise-induced Abstract 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