Noradrenaline Reuptake Inhibition Impairs Cortical Output and Limits Endurance Time

To assess the neural mechanisms that limit endurance time, we compared a fatiguing task performed under the influence of reboxetine (REB), a noradrenaline reuptake inhibitor, and placebo (PLA).

Nine male subjects (age = 24 ± 2 yr) participated in this study. The fatiguing task involved repeated 3-s submaximal isometric contractions of the knee extensors (∼33% maximal voluntary contraction) with a 2-s rest between each contraction and performed until task failure. Before, during, and after exercise, changes in voluntary activation, corticospinal (motor-evoked potential) and spinal excitability (Hoffman reflex), and muscle contractile properties were tested using electrical and transcranial magnetic stimulations. A psychomotor vigilance task assessed reaction time before and after exercise.

Compared with PLA, REB reduced the endurance time by 15.6% (P = 0.04). The maximal voluntary contraction torque decreased to a similar extent at task failure in both conditions (P < 0.01), whereas the rate of decline was greater in REB than that in PLA (P = 0.02). The level of voluntary activation tested by transcranial magnetic stimulation and electrical stimulation decreased (P < 0.01) by 10%-15% at the end of the task, but the mean rate of decline was greater in REB (P ≤ 0.03). Although motor-evoked potential did not change during fatigue, Hoffman reflex, and electrically evoked torque decreased similarly in the PLA and REB conditions (P ≤ 0.02). After exercise, reaction time increased by 3.5% (P = 0.02) in REB but did not change in the PLA condition.

These findings suggest that because of the noradrenaline reuptake inhibition, the output from the motor cortex is decreased at a greater rate than that in the PLA condition, contributing thereby to shorten endurance time.