Acute norepinephrine reuptake inhibition decreases performance in normal and high ambient temperature

Abstract

Combined inhibition of dopamine (DA)/norepinephrine (NE) reuptake improves exercise performance and increases core temperature in the heat. A recent study demonstrated that this effect may primarily be related to increased DA activity. NE reuptake inhibition (NERI), however, has received little attention in humans, certainly in the heat, where central fatigue appears to be a main factor influencing performance. Therefore the present study examines the effect of NERI (reboxetine) on exercise capacity, thermoregulation, and hormonal response in normal and high temperature. Nine healthy well-trained male cyclists participated in this study. Subjects ingested either placebo (Pla; 2 x 8 mg) or reboxetine (Rebox; 2 x 8 mg). Subjects exercised in temperate (18 degrees C) or warm (30 degrees C) conditions and cycled for 60 min at 55% W(max) immediately followed by a time trial (TT; Pla18/Rebox18; Pla30/Rebox30) to measure exercise performance. Acute NERI decreased power output and consequently exercise performance in temperate (P = 0.018) and warm (P = 0.007) conditions. Resting heart rate was significantly elevated by NERI (18 degrees C: P = 0.02; 30 degrees C: P = 0.018). In Rebox18, heart rate was significantly higher than in the Pla18, while in the heat no effect of the drug treatment was reported during exercise. In Rebox30, all hormone concentrations increased during exercise, except for growth hormone (GH), which was significantly lower during exercise. In Rebox18, prolactin (PRL) concentrations were significantly elevated; GH was significantly higher at rest, but significantly lower during exercise. In conclusion, manipulation of the NE system decreases performance and modifies hormone concentrations, thereby indicating a central NE effect of the drug. These findings confirm results from previous studies that predominantly increased DA activity is important in improving performance.

The Involvement of Brain Monoamines in the Onset of Hyperthermic Central Fatigue

“…The inhibitory effect exerted by noradrenaline on physical performance, even though it was not accompanied by a significant change in body temperature, induced a tendency for hypothermia. This inclination was further corroborated by thermal stress scale scores that indicated a cold sense by the subjects after noradrenaline reuptake inhibition (Roelands et al, 2008). Studies have provided conflicting data about the role of noradrenaline in thermoregulation.…”

“…The administration of reboxetine, a noradrenaline reuptake inhibitor, led to a trend towards a decrease in exercise performance in well-trained endurance athletes (Piacentini et al, 2002). This response was later confirmed by Roelands et al (2008), who suggested that an increase in the concentration of noradrenaline could be unfavorable for exercise performance because treatment with the noradrenaline reuptake inhibitor decreased physical capacity in both normal and high ambient temperatures. The inhibitory effect exerted by noradrenaline on physical performance, even though it was not accompanied by a significant change in body temperature, induced a tendency for hypothermia.…”

“…Although noradrenaline is associated with arousal, consciousness and reward mechanisms in the brain (Roelands & Meeusen, 2010), researchers have shown that elevated brain levels of this catecholamine has a negative effect on exercise performance (Piacentini et al, 2002;Roelands et al, 2008;Roelands & Meeusen, 2010). The administration of reboxetine, a noradrenaline reuptake inhibitor, led to a trend towards a decrease in exercise performance in well-trained endurance athletes (Piacentini et al, 2002).…”

Role of Central Fatigue in Resistance and Endurance Exercises: An Emphasis on Mechanisms and Potential Sites

“…Furthermore, recent studies have shown that the increased noradrenalin concentration may be unfavorable for exercise performance (Roelands et al, 2008). Administration of Reboxetine, NA reuptake inhibitor, decreased performance in normothermia (Piacentini et al, 2002).…”

“…Researchers have shown that in optimal environment conditions for thermal exchange in which temperature of skin remains fairly low during the 8 km running, achieving to the critical core temperature (40° C) doesn't reduce running speed (Meeusen & Roelands, 2010). Finally, 70 pharmacological manipulation to increase DA has indicated along with performance improvement, core temperature of the individuals surpasses 40° C (Roelands et al, 2008;Watson et al, 2005). From this point of view, the critical core temperature should not be considered an all-or-none phenomenon, but it's better to be considered as a continuum with the complex interaction of various physiological systems (Meeusen & Roelands, 2010).…”