It has been reported that exercise increases brain tryptophan (TRP), which is related to exhaustive fatigue. To study this further, the effect of increased TRP availability on the central nervous system (CNS) with regard to mechanical efficiency, oxygen consumption (VO2) and runtime to exhaustion was studied in normal untrained rats. Each rat was anesthetized with thiopental (30 mg/kg ip b. wt.) and fitted with a chronic guiding cannula attached to the right lateral cerebral ventricle I week prior to the experiments. Immediately before exercise, the rats were randomly injected through these cannulae with 2.0 mul of 0.15 M NaCl (n = 6) or 20.3 muM L-TRP solution (n = 6). Exercise consisted of running on a treadmill at 18 m min(-1) and 5% inclination until exhaustion. TRP-treated rats presented a decrease in their mechanical efficiency (21.25 +/- 0.84%, TRP group vs. 24.31 +/- 0.98%, saline-treated group; P less than or equal to.05), and increased VO2 at exhaustion (40.3 +/- 1.6 ml kg(-1) min(-1), TRP group vs. 36.0 +/- 0.8 ml kg(-1) min(-1), saline group; P less than or equal to .05), indicating that the metabolic cost of exercise was higher in the former group. In addition, a highly significant reduction was also observed in run-time to exhaustion of TRP animals compared to those of the saline-treated group (15.2 +/- 1.52 min, TRP group vs. 50.6 +/- 5.4 min, saline group; P less than or equal to.0001). It can be deduced from the data that intracerebroventricular TRP injection in rats increases 02 consumption and reduces mechanical efficiency during exercise, diminishing running performance. (C) 2002 Elsevier Science Inc. All rights reserved.