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

Department of Human Physiology and Sports Medicine, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium.
Journal of Applied Physiology (Impact Factor: 3.06). 08/2008; 105(1):206-12. DOI: 10.1152/japplphysiol.90509.2008
Source: PubMed


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.

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Available from: Bart Roelands
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    • "MDMA or placebo was administered at 12:00 p.m., 4 and 16 h after duloxetine. Reboxetine and duloxetine were administered twice at high doses to obtain peak plasma concentrations of (mean ± SD) 372±34 and 107±10 ng/ml, respectively, similar to the concentrations reached with chronic daily administration of 4 and 60 mg of the drugs, respectively (Hysek et al. 2011; Simmler et al. 2011), and as previously used to manipulate noradrenergic function in healthy subjects (Roelands et al. 2008). Compliance with the first administration of reboxetine and duloxetine on the evening prior to the test day was confirmed analytically in plasma (Hysek et al. 2011, 2012d). "
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    ABSTRACT: Rationale Pupillometry can be used to characterize autonomic drug effects. Objective This study was conducted to determine the autonomic effects of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), administered alone and after pretreatment with reboxetine, duloxetine, clonidine, carvedilol, and doxazosin, on pupillary function. Methods Infrared pupillometry was performed in five placebo-controlled randomized studies. Each study included 16 healthy subjects (eight men, eight women) who received placebo–MDMA (125 mg), placebo–placebo, pretreatment–placebo, or pretreatment–MDMA using a crossover design. Results MDMA produced mydriasis, prolonged the latency, reduced the response to light, and shortened the recovery time. The impaired reflex response was associated with subjective, cardiostimulant, and hyperthermic drug effects and returned to normal within 6 h after MDMA administration when plasma MDMA levels were still high. Mydriasis was associated with changes in plasma MDMA concentration over time and longer-lasting. Both reboxetine and duloxetine interacted with the effects of MDMA on pupillary function. Clonidine did not significantly reduce the mydriatic effects of MDMA, although it produced miosis when administered alone. Carvedilol and doxazosin did not alter the effects of MDMA on pupillary function. Conclusions The MDMA-induced prolongation of the latency to and reduction of light-induced miosis indicate indirect central parasympathetic inhibition, and the faster recovery time reflects an increased sympathomimetic action. Both norepinephrine and serotonin mediate the effects of MDMA on pupillary function. Although mydriasis is lasting and mirrors the plasma concentration–time curve of MDMA, the impairment in the reaction to light is associated with the subjective and other autonomic effects of MDMA and exhibits acute tolerance.
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    • "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. "

    Full-text · Chapter · Feb 2012
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    • "MDMA or placebo was administered at 12:00 hours, 4 and 16 h after duloxetine. Reboxetine and duloxetine were administered twice in high doses to obtain plasma concentrations similar to those reached with chronic daily administrations of the drugs and as previously used to manipulate the norepinephrine function in healthy subjects (Roelands et al. 2008). In the clonidine- MDMA study, clonidine (150 μg, Catapresan; Boeringer Ingelheim, Basel, Switzerland) or identical placebo (lactose) was administered at 8:00 hours, 1 h before MDMA or placebo (9:00 hours). "
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