Influence of Paroxetine, Branched-Chain Amino Acids and Tyrosine on Neuroendocrine System Responses and Fatigue in Humans

Abstract

Effects of a serotonin re-uptake inhibitor and oral amino acid supplementations on physical and mental performance as well as neuroendocrine variables were investigated. 10 male subjects cycled in four trials until exhaustion. Participants ingested a placebo in trial (T) I, 20 mg paroxetine in T II, 21 g branched-chain amino acids (BCAA) in I Ill and 20 g tyrosine (TYR) in T IV. Heart rate, capillary lactate, plasma insulin, free fatty acids, glucose, serotonin and fI-endorphine did not differ in trials. Plasma ammonia increments during exercise were higher in T Ill. Plasma BCAA in T Ill and plasma TYR in T IV were increased after 30 mm of exercise according to the supplemented substances. In contrast to all other trials, the ratio of plasma free TRP/BCAA did not increase in T Ill. Plasma TYR/BCAA was augmented in I IV and decreased in T III after 30 mm of exercise, whereas it did not change in I I and II. Plasma prolactin (PRL), growth hormone, cortisol, adrenocorticotropic hormone, norepinephrine and epinephrine increased during all trials. Plasma PRL increments were higher in I IV. Exhaustion was reached earlier in I II. No significant differences were found between other trials. Drive during psychometric testing subsequent to exercise was improved in I III and IV. The results indicate that fatigue during endurance exercise was increased by pharmacological augmentation of the brain serotonergic activity. However, a reduction of 5-HI synthesis via BCAA supplementation did not affect physical fatigue. TYR administration did not alter physical performance either although plasma PRI increments suggest that changes in the monoaminergic system were induced. Precaution is necessary before assuming an ergogenic value of amino acids.

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.…”

Oral branched-chain amino acid supplements that reduce brain serotonin during exercise in rats also lower brain catecholamines

“…Hence, TYR hydroxylase is much closer to substrate saturation than is TRP hydroxylase and precursorinduced increases in overall synthesis in the catecholamine pathway would be expected to be smaller than those in the 5HT pathway. This may account for the variable effects of TYR administration previously observed on physical performance and mental function in soldiers and athletes (Struder et al 1998;Lieberman 2003;Tumilty et al 2011;Watson et al 2012). However, since TYR hydroxylase is not fully saturated with substrate (Carlsson and Lindqvist 1978), the above considerations would also predict that reducing brain TYR concentrations might elicit a large reduction in catecholamine biosynthesis.…”

“…Human and rat studies exploring for effects of drugs that increase 5HT synaptic transmission in brain have reported that elevating 5HT transmission reduces physical erformance (Wilson and Maughan 1992;Bailey et al 1992Bailey et al , 1993Struder et al 1998). Conversely, drugs that increase catecholamine transmission enhance physical performance (Roelands et al 2008a, b).…”

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

“…Reduced exercise performance related to higher serotonin content in the preoptic area and the hypothalamus was also verified after a central blockade of angiotensinergic synapses . Serotonin reuptake inhibitors have also been widely used, with the purpose of investigating the relationship between the neurotransmitter and central fatigue (Meeusen et al, 2001;Pannier et al, 1995;Parise et al, 2001;Struder et al, 1998; W. M. Wilson et al, 1992). However, the results are contradictory and inconclusive.…”

“…However, the results are contradictory and inconclusive. Although data have demonstrated no effect of different serotonin reuptake inhibitors (pizotifen, fluoxetine, citalopam) on exercise performance in humans (Meeusen et al, 2001;Pannier et al, 1995;Parise et al, 2001;Roelands et al, 2009;Strachan et al, 2004), findings from Struder et al (1998) and W. M. Wilson et al (1992) indicate that fatigue occurs sooner with pharmacological augmentation of the brain's serotonergic activity by serotonin re-uptake inhibitor (paroxetine) supplements. These different outcomes might be explained by divergent exercise protocols, pharmacological manipulations, drug receptor specificity and drug dosages.…”