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Background  The present experiment examined the responses of peripheral modulators and indices of brain serotonin (5-HT) and dopamine (DA) function and their association with perception of effort during prolonged exercise in the heat after creatine (Cr) supplementation.    Methods  Twenty one endurance-trained males performed, in a double-blind fashion, two constant-load exercise tests to exhaustion at 63 ± 5%V  ˙O  2 max  in the heat (ambient temperature: 30.3 ± 0.5 °C, relative humidity: 70 ± 2%) before and after 7 days of Cr (20 g·d -1  Cr + 140 g·d -1  glucose polymer) or placebo (Plc) (160 g·d -1  glucose polymer) supplementation.    Results  3-way interaction has shown that Cr supplementation reduced rectal temperature, heart rate, ratings of perceived leg fatigue ( P  < 0.05), plasma free-tryptophan (Trp) ( P  < 0.01) and free-Trp:tyrosine ratio ( P  < 0.01) but did not influence the ratio of free-Trp:large neutral amino acids or contribute in improving endurance performance (Plc group, n = 10: 50.4 ± 8.4 min vs. 51.2 ± 8.0 min,  P  > 0.05; Cr group, n = 11: 47.0 ± 4.7 min vs. 49.7 ± 7.5 min,  P  > 0.05). However, after dividing the participants into "responders" and "non-responders" to Cr, based on their intramuscular Cr uptake, performance was higher in the "responders" relative to "non-responders" group (51.7 ± 7.4 min vs.47.3 ± 4.9 min,  p  < 0.05).    Conclusion  although Cr influenced key modulators of brain 5-HT and DA function and reduced various thermophysiological parameters which all may have contributed to the reduced effort perception during exercise in the heat, performance was improved only in the "responders" to Cr supplementation. The present results may also suggest the demanding of the pre-experimental identification of the participants into "responders" and "non-responders" to Cr supplementation before performing the main experimentation. Otherwise, the possibility of the type II error may be enhanced.

Brain serotonin and dopamine modulators, perceptual responses and endurance performance during exercise in the heat following creatine supplementation