There is mounting evidence that increased brain serotonin during exercise is associated with the onset of CNS-mediated fatigue. Serotonin receptor sensitivity is likely to be an important determinant of this fatigue. Alterations in brain serotonin receptor sensitivity were examined in Wistar rats throughout 6 weeks of exercise training. A test group of rats completed endurance training on a treadmill 4 times per week and completed 2 exercise tests per week. Receptor sensitivity was determined indirectly as the reduction in exercise time in response to a dose of a serotonin (1A) agonist, m-Chlorophenylpiperazine (m-CPP). Two groups of controls were used to examine i) the effect of the injection per se on exercise performance and ii) changes in serotonin receptor sensitivity associated with maturation.

In the test group, undrugged exercise performance significantly improved by 49% after 6 weeks of training (4455 ± 636 s to 6642 ± 692 s, p=0.03). Drugged exercise performance also increased significantly from week 1 to week 6 (260 ± 31 s. to 679 ± 179 s, p<0.001). Control group results indicated the dose of m-CPP alone caused fatigue during exercise tests and that maturation was not responsible for the change in receptor sensitivity. There was also a significant relationship (p<0.05) between receptor sensitivity and undrugged endurance performance in the first two weeks of training. That is, the rats that tolerated the drug well also demonstrated superior endurance performance.

Improved resistance to the fatiguing effects of the serotonin agonist suggests desensitisation of central serotonin receptors, probably the 5-HT1A receptors. Endurance training appears to stimulate an adaptive response to the fatiguing effects of increased brain serotonin, which may enhance endurance exercise performance. This finding is supported by the relationship between receptor sensitivity and undrugged endurance performance