Endurance Performance in Humans: The Effect of a Dopamine Precursor or a Specific Serotonin (5-HT_2A/2C) Antagonist

Abstract

In this study we examined the effect of a dopamine (DA) precursor (L-DOPA) or a serotonin (5-HT) antagonist (Ritanserin) on time to exhaustion. The study had a double-blind, randomised, placebo controlled and cross-over design. Seven moderately trained men performed three tests to exhaustion at 65% Wattmax. Each test was separated by two weeks to allow washout of the drugs (dose: 4 mg/kg Sinemet, and 0.3 mg/kg Ritanserin). Blood lactate, hematocrit, glucose, ammonia, free fatty acids (FFA), growth hormone (GH) and catecholamines were determined before and after exercise. Time to exhaustion did not differ between the three trials. Most of the parameters measured in this study responded as predicted during cycling to exhaustion in man. DA agonism significantly increased heart rate, lactate, and plasma DA values at rest, while other parameters such as FFA, lactate, plasma noradrenaline (NA) and adrenaline (A), and plasma GH showed the highest absolute levels at exhaustion. Ritanserin did not influence basal glucose and heart rate at rest, but this group showed a much lower increase in plasma catecholamine levels. We conclude that under the present conditions, neither a metabolic precursor of DA nor a specific centrally acting 5-HT2A/2C antagonist, when given in two single doses 24 h and immediately before the experiments, influences the time to exhaustion on a bicycle trial at 65% Wattmax.

Acute dopamine/noradrenaline reuptake inhibition enhances human exercise performance in warm, but not temperate conditions

“…• C in the present study supports the findings of recent investigations of nutritional and pharmacological manipulation of catecholaminergic neurotransmission (Meeusen et al 1997;Struder et al 1998;Chinevere et al 2002;Piacentini et al 2004). Recently the influence of bupropion on exercise performance and the hormonal response to a 90 min TT has been investigated (Piacentini et al 2004).…”

The Effects of Acute Dopamine Reuptake Inhibition on Performance

“…It appears that this response is accompanied by an increased core temperature and heart rate, but with the same perception of effort and thermal stress. Similarly these and other studies that used nutritional and pharmacological manipulations of catecholaminergic neurotransmission confirmed the lack of performance improvements in 18°C (13,21,24,27,30), suggesting that dopaminergic neurotransmission may only have a significant role in fatigue when exercise is undertaken in warm environmental temperatures.…”

Performance in the Heat—Physiological Factors of Importance for Hyperthermia‐Induced Fatigue

“…Cocaine acts as a serotonin-norepinephrinedopamine reuptake inhibitor and similarly amphetamine exerts its effects by modulating several neurotransmitters in the brain (241). Therefore, studies with specific effects on either the serotonergic or the dopaminergic systems have been conducted to elucidate the exact influence from either system (169,174,(220)(221)(222). However, in temperate environments a number of exercise studies with human subjects have failed to show any clear performance enhancing effects of elevating extracellular dopamine levels via dopamine reuptake inhibitors or through attempted alterations in cerebral serotonin levels via nutritional or medical manipulations (171,174,221,239,314).…”

“…197 for explanation of the possible effect of BCAA ingestion on cerebral tryptophan uptake) does not affect performance during exercise in the heat in nonfasting subjects (43) and even in glycogendepleted subjects where plasma fatty acid as well as free tryptophan levels are high and fatigue aggravated, BCAA supplementation fails to affect performance (315). The influence of serotonergic activity during exercise in the heat has also been evaluated with serotonin reuptake inhibitors (293) or a selective 5-HT receptor antagonist (173) and it appears that blockade of 5-HT receptors to a minor extent may aggravate hyperthermia during exercise in the heat, but neither inhibition of serotonin reuptake nor administration of receptor antagonists affected performance (241,292). Serotonergic neurons are involved with both thermoregulation and motor activation, consequently they may play an important role during exercise in hot environments (126), but it appears that the alterations in serotonergic activity induced by the various pharmacological interventions are not of such magnitude that they alter exercise performance.…”