Evidence for a possible role of 5‐hydroxytryptamine in the genesis of fatigue in man: administration of paroxetine, a 5‐HT re‐uptake inhibitor, reduces the capacity to perform prolonged exercise

Wilson, W. M.; Maughan, R. J.

doi:10.1113/expphysiol.1992.sp003660

Cited by 194 publications

(123 citation statements)

References 6 publications

Supporting

Mentioning

111

Contrasting

Unclassified

Order By: Relevance

“…Our results are also consistent with pharmacological studies performed in humans. It was demonstrated that oral intake of the 5-HT 1A receptor agonist buspirone or the selective serotonin reuptake inhibitor paroxetine trigger faster exhaustion during motor tasks (14,15). Moreover, during central fatigue, the gain of MNs is reduced (5, 8).…”

Section: Discussionmentioning

confidence: 99%

“…However, evidence suggests that central fatigue correlates with increased levels of serotonin (5-HT) in the CNS. Human subjects that perform an intense motor task are faster exhausted after intake of a 5-HT 1A receptor agonist (14) or a selective serotonin reuptake inhibitor (15). In animals, injection of the 5-HT precursor tryptophan in the blood or directly in the CNS accelerates the exhaustion occurring during motor activity (16,17).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation

Cotel

Exley

Cragg

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

133

141

View full text Add to dashboard Cite

Motor fatigue induced by physical activity is an everyday experience characterized by a decreased capacity to generate motor force. Factors in both muscles and the central nervous system are involved. The central component of fatigue modulates the ability of motoneurons to activate muscle adequately independently of the muscle physiology. Indirect evidence indicates that central fatigue is caused by serotonin (5-HT), but the cellular mechanisms are unknown. In a slice preparation from the spinal cord of the adult turtle, we found that prolonged stimulation of the raphespinal pathway-as during motor exercise-activated 5-HT 1A receptors that decreased motoneuronal excitability. Electrophysiological tests combined with pharmacology showed that focal activation of 5-HT 1A receptors at the axon initial segment (AIS), but not on other motoneuronal compartments, inhibited the action potential initiation by modulating a Na + current. Immunohistochemical staining against 5-HT revealed a high-density innervation of 5-HT terminals on the somatodendritic membrane and a complete absence on the AIS. This observation raised the hypothesis that a 5-HT spillover activates receptors at this latter compartment. We tested it by measuring the level of extracellular 5-HT with cyclic voltammetry and found that prolonged stimulations of the raphe-spinal pathway increased the level of 5-HT to a concentration sufficient to activate 5-HT 1A receptors. Together our results demonstrate that prolonged release of 5-HT during motor activity spills over from its release sites to the AIS of motoneurons. Here, activated 5-HT 1A receptors inhibit firing and, thereby, muscle contraction. Hence, this is a cellular mechanism for central fatigue.movement | spike genesis | input-output gain | movement control P rolonged physical activity leads to motor fatigue (1, 2). The force produced by muscles decreases in part because of the lack of glycogen (3) in the muscle and/or failures at the neuromuscular junctions (4). In addition to this well-described muscle fatigue, motor fatigue also involves an element originating in the CNS (5-8). This "central fatigue" is characterized by a decreased ability to contract the muscle fibers adequately during a motor activity and is observed independently of the muscle fatigue (6). It is often studied during maximal voluntary contractions (5, 6, 9). Nevertheless, it is also present during weak physical contraction (1,2,8,(10)(11)(12). Central fatigue secures rotation of motor units (13) and prevents hyperactivity of muscles (6). Elements of central fatigue involve the cortex (6), and the spinal cord at the level of motoneurons (MNs) (5).The cellular mechanisms responsible for a decrease of the activity of MNs remain unknown. However, evidence suggests that central fatigue correlates with increased levels of serotonin (5-HT) in the CNS. Human subjects that perform an intense motor task are faster exhausted after intake of a 5-HT 1A receptor agonist (14) or a selective serotonin reuptake inhibitor (15). In animals, inject...

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation

Cotel

Exley

Cragg

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

133

141

View full text Add to dashboard Cite

show abstract

“…While there is some experimental support for the hypothesis of Newsholme & Castell (2000), the evidence of a beneficial effect on exercise performance is limited. Nonetheless, the fact that pharmacological manipulation of 5-hydroxytryptamine activity can alter exercise performance (Wilson & Maughan, 1992) does suggest that nutritional interventions to produce the same effect may also be possible.…”

Section: Central Nervous System Effectsmentioning

confidence: 99%

The athlete’s diet: nutritional goals and dietary strategies

Maughan

2002

Proc. Nutr. Soc.

View full text Add to dashboard Cite

When talented, motivated and highly trained athletes meet for competition the margin between victory and defeat is usually small. When everything else is equal, nutrition can make the difference between winning and losing. Although the primary concern of many athletes is to supplement the diet with protein, vitamins and minerals, and a range of more exotic compounds, key dietary issues are often neglected. Athletes must establish their nutritional goals, and must also be able to translate them into dietary strategies that will meet these goals. Athletes are often concerned with dietary manipulations in the period around competition, but the main role of nutrition may be to support consistent intensive training which will lead to improved performance. Meeting energy demand and maintaining body mass and body fat at appropriate levels are key goals. An adequate intake of carbohydrate is crucial for maintaining muscle glycogen stores during hard training, but the types of food and the timing of intake are also important. Protein ingestion may stimulate muscle protein synthesis in the post-exercise period, promoting the process of adaptation in the muscles. Restoration of fluid and electrolyte balance after exercise is essential. If energy intake is high and a varied diet is consumed, supplementation of the diet with vitamins and minerals is not warranted, unless a specific deficiency is identified. Specific strategies before competition may be necessary, but this requirement depends on the demands of the sport. Generally, it is important to ensure high pre-competition glycogen stores and to maintain fluid balance. There is limited evidence to support the use of dietary supplements, but some, including perhaps creatine and caffeine, may be beneficial.

show abstract

“…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).…”

mentioning

confidence: 99%

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

et al. 2013

View full text Add to dashboard Cite

Exercise raises brain serotonin release and is postulated to cause fatigue in athletes; ingestion of branched-chain amino acids (BCAA), by competitively inhibiting tryptophan transport into brain, lowers brain NOT THE PUBLISHED VERSION; this is the author's final, peer-reviewed manuscript. The published version may be accessed by following the link in the citation at the bottom of the page.Amino Acids, Vol. 45, No. 5 (November 2013): pg. 1133-1142. DOI. This article is © Springer and permission has been granted for this version to appear in e-Publications@Marquette. Springer does not grant permission for this article to be further copied/distributed or hosted elsewhere without the express permission from Springer.2 tryptophan uptake and serotonin synthesis and release in rats, and reputedly in humans prevents exercise-induced increases in serotonin and fatigue. This latter effect in humans is disputed. But BCAA also competitively inhibit tyrosine uptake into brain, and thus catecholamine synthesis and release. Since increasing brain catecholamines enhances physical performance, BCAA ingestion could lower catecholamines, reduce performance and thus negate any serotonin-linked benefit. We therefore examined in rats whether BCAA would reduce both brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Sedentary and exercising rats received BCAA or vehicle orally; tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis rates were measured 1 h later in hypothalamus. BCAA reduced hypothalamic tryptophan and tyrosine concentrations, and serotonin and catecholamine synthesis. These reductions in tyrosine concentrations and catecholamine synthesis, but not tryptophan or serotonin synthesis, could be prevented by co-administering tyrosine with BCAA. Complete essential amino acid mixtures, used to maintain or build muscle mass, were also studied, and produced different effects on hypothalamic tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Since pharmacologically increasing brain catecholamine function improves physical performance, the finding that BCAA reduce catecholamine synthesis may explain why this treatment does not enhance physical performance in humans, despite reducing serotonin synthesis. If so, adding tyrosine to BCAA supplements might allow a positive action on performance to emerge.

show abstract

Evidence for a possible role of 5‐hydroxytryptamine in the genesis of fatigue in man: administration of paroxetine, a 5‐HT re‐uptake inhibitor, reduces the capacity to perform prolonged exercise

Cited by 194 publications

References 6 publications

Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation

Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation

The athlete’s diet: nutritional goals and dietary strategies

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

Contact Info

Product

Resources

About