Physical exercise-induced fatigue: the role of serotonergic and dopaminergic systems

Abstract

Brain serotonin and dopamine are neurotransmitters related to fatigue, a feeling that leads to reduced intensity or interruption of physical exercises, thereby regulating performance. The present review aims to present advances on the understanding of fatigue, which has recently been proposed as a defense mechanism instead of a "physiological failure" in the context of prolonged (aerobic) exercises. We also present recent advances on the association between serotonin, dopamine and fatigue. Experiments with rodents, which allow direct manipulation of brain serotonin and dopamine during exercise, clearly indicate that increased serotoninergic activity reduces performance, while increased dopaminergic activity is associated with increased performance. Nevertheless, experiments with humans, particularly those involving nutritional supplementation or pharmacological manipulations, have yielded conflicting results on the relationship between serotonin, dopamine and fatigue. The only clear and reproducible effect observed in humans is increased performance in hot environments after treatment with inhibitors of dopamine reuptake. Because the serotonergic and dopaminergic systems interact with each other, the serotonin-to-dopamine ratio seems to be more relevant for determining fatigue than analyzing or manipulating only one of the two transmitters. Finally, physical training protocols induce neuroplasticity, thus modulating the action of these neurotransmitters in order to improve physical performance.

Figure 1.. The pharmacological blockade of serotonin synthesis prevents the reduction in physical performance induced by central administration of the serotonin precursor, tryptophan (TRP). The figure shows the effect of intracerebroventricular (icv) injections of TRP or saline (SAL) on time to fatigue in rats pretreated with intraperitoneal (ip) SAL or p-chlorophenylalanine (p-CPA) and that underwent submaximal physical exercise until they were fatigued. Data are reported as means±SE. The number of animals is indicated in parentheses. ^#P<0.05, significantly different from SAL ip + SAL icv; ^§P<0.001, significantly different from SAL ip + TRP icv. This figure is reprinted with permission from Cordeiro et al., 2014 (12).

Figure 2.. Physical performance is associated with central concentrations of serotonin (5-HT) in rats. The figure shows the significant correlation between the time to fatigue and 5-HT concentrations in the preoptic area in rats that received an intracerebroventricular injection of 2 µL tryptophan (TRP, black circles) or saline (SAL, white circles). This figure is reprinted with permission from Soares et al., 2007 (29).

Figure 3.. The inhibition of serotonin reuptake affects physical performance in the subjects with higher aerobic capacity but not in those with lower aerobic capacity. The figure shows the time to fatigue by the subjects with lower (panel A) and higher (panel B) aerobic capacity during cycling at 60% of their maximal power output. Each subject participated in four experimental trials with the following drug conditions: placebo and 10, 20, and 40 mg of paroxetine. Data are reported as means±SE. *P<0.05, significantly different from individuals with low aerobic capacity. ^#P<0.05, significantly different from the placebo. This figure is reprinted with permission from Teixeira-Coelho et al. 2014 (43).

Figure 4.. Concentrations of dopaminergic variables in the caudate–putamen at rest and after moderate-intensity exercise (ME) in rats with low (LP), standard (SP) and high (HP) performances. The figure shows the concentrations of 3,4-dihydroxyphenylacetic acid-to-dopamine (DOPAC/DA) ratio. Data are reported as means±SE. *P<0.05, **P<0.01 compared to rest.⁺P<0.05 compared to LP. ^#P<0.05 compared to SP. This figure is reprinted with permission from Rabelo et al., 2015 (72).

Figure 5.. Motor and psycho-physiological effects induced by monoamines in the central nervous system that modulate fatigue during aerobic exercises.