Effects of noradrenaline and dopamine on supraspinal fatigue in well-trained men

PURPOSE: Prolonged exhaustive exercise induces a failure of the nervous system to activate the involved muscles maximally (i.e., central fatigue). Part of central fatigue may reflect insufficient output from the motor cortex (i.e., supraspinal fatigue), but the cause is unresolved. To investigate the potential link between supraspinal fatigue and changes in brain concentration of dopamine and noradrenaline in temperate environment, we combined neurophysiological methods and pharmacological manipulation of these two neurotransmitters. METHODS: Changes in performance of a cycling exercise (time trial [TT]) were tested after oral administration of placebo (Pla), dopamine, or noradrenaline reuptake inhibitors (methylphenidate and reboxetine [Rebox], respectively) in well-trained male subjects. Changes in voluntary activation, corticospinal excitability, and muscle contractile properties were tested in the knee extensors using transcranial magnetic stimulation and motor nerve electrical stimulation before and after exercise. A psychomotor vigilance task (PVT) was also performed. RESULTS: Compared with Pla, methylphenidate did not affect exercise performance (P = 0.19), but more time was needed to complete the TT after administration of Rebox (approximately 9%, P < 0.05). For the latter condition, the reduced performance was accompanied by a central/supraspinal fatigue (5%-6%, P < 0.05) and worsened PVT performance (7%, P < 0.05). For the three conditions, corticospinal excitability was unchanged, and peripheral fatigue was similar. Because the ingestion of Rebox induced a greater decrease in voluntary activation and PVT performance after the TT than Pla, with no modification in corticospinal excitability, the noradrenaline reuptake inhibitor likely affected supraspinal circuits located before the motor cortex. CONCLUSION: These results suggest that noradrenaline, but not dopamine reuptake inhibition, contributes to the development of central/supraspinal fatigue after a prolonged cycling exercise performed in temperate conditions.