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.

Effects of a commercially available branched-chain amino acid-alanine-carbohydrate-based sports supplement on perceived exertion and performance in high intensity endurance cycling tests

“…Supplementation with BCAA has been proposed as a possible strategy to limit the development of central fatigue [5], in particular, in endurance events [1]. Central fatigue, which pertains to the central nervous system (CNS), is a complex phenomenon arising under conditions of low energy availability [6,7], ammonia accumulation in blood and tissues [8], and changes in neurotransmitter synthesis -in particular, an increase in serotonin and a decrease in dopamine -which causes a state of increasing tiredness during exhaustive exercise [9]. The presence of elevated cerebral serotonin levels observed in rats under fatigue [10], is the basis of a well-accepted theory to account for the onset/increase of central fatigue in humans as well.…”

Rats with higher intrinsic exercise capacities exhibit greater preoptic dopamine levels and greater mechanical and thermoregulatory efficiencies while running

“…This phenomenon has been accepted as a protective mechanism that prevents the organism from achieving a physiological condition that would result in tissue damage (30). Depending on the environmental conditions (14,40) and some physical exercise features, e.g., intensity and duration (39,49), fatigue can be differentially influenced by alterations in multiple physiological responses that signal early exercise cessation, including hyperthermia (4,(31)(32)(33), degradation of energy substrates (17), and changes in the levels of neurotransmitters (7,8,13,53). Regarding the thermoregulatory influence on exercise fatigue, the increased heat production by the contracting muscles requires activation of heat loss mechanisms to maintain the core body temperature in a range compatible with physical performance and even life (51).…”

Exercise-Induced Adaptations to the Mouse Striatal Adenosine System

“…The immunohistochemistry assessment of protein density provides some evidence that striatal A 1 R and A 2A R concentrations are affected by physical activity status, which could reduce antagonistic heteromeric interactions with dopamine receptors in the striatum. Together, these data provide a potential mechanism in support of exercise-facilitated dopaminergic function in the striatum [67,[72][73][74].…”