[1][2][3][4] In healthy individuals, central fatigue can occur from prolonged exercise and is associated with neurochemical changes in the brain, involving (but not limited to) serotonin (5-HT), noradrenaline, and dopamine.
[2][3][4] The roles of dopamine, noradrenaline, and serotonin in CNS fatigue are unclear, as pharmacological manipulation of these systems has yielded mixed results.
Existing experimental methods have provided enough evidence to suggest that variations in synaptic serotonin, noradrenaline, and dopamine are significant drivers of central nervous system fatigue.
[2][3][4] Paradoxically, however, direct dopamine agonists such as bromocriptine and pramipexole have caused opposite, pro-fatigue effects in healthy humans.
The transport mechanism for tryptophan is shared with the branched chain amino acids (BCAAs), leucine, isoleucine, and valine.
During extended exercise, BCAAs are consumed for skeletal muscle contraction, allowing for greater transport of tryptophan across the blood–brain barrier.
None of the components of the serotonin synthesis reaction are saturated under normal physiological conditions,[10] allowing for the increased production of the neurotransmitter.
This may be due to a counter-acting mechanism: BCAAs also limit the uptake of tyrosine, another aromatic amino acid, like tryptophan.
In addition to fuel, many athletes consume performance-enhancing drugs including stimulants in order to boost their abilities.
This could not be explained by the varying levels of muscle glycogen; however, higher plasma glucose concentration may have led to this result.
Dr. Stephen Bailey posits that the central nervous system can sense the influx of carbohydrates and reduces the perceived effort of the exercise, allowing for greater endurance capacity.
[25] Several studies have attempted to decrease the synthesis of serotonin by administering branched-chain amino acids and inhibiting the transport of tryptophan across the blood brain barrier.
[7] Central nervous system fatigue is a key component in preventing peripheral muscle injury.
This is crucial in order to protect the homeostasis of the body and to keep it in a proper physiological state capable of full recovery.
Protecting organs from potentially dangerous core temperatures and nutritional lows is an important brain function.
Central nervous system fatigue alerts the athlete when physiological conditions are not optimal so either rest or refueling can occur.