ç ois Haas. Effect of naloxone on perceived exertion and exercise capacity during maximal cycle ergometry. J Appl Physiol 93: 2023-2028, 2002. First published August 23, 2002 10.1152/japplphysiol.00521.2002We assessed the effects of naloxone, an opioid antagonist, on exercise capacity in 13 men and 5 women (mean age ϭ 30.1 yr, range ϭ 21-35 yr) during a 25 W/min incremental cycle ergometer test to exhaustion on different days during familiarization trial and then after 30 mg (iv bolus) of naloxone or placebo (Pl) in a double-blind, crossover design. Minute ventilation (V E), O2 consumption (V O2), CO2 production, and heart rate (HR) were monitored. Perceived exertion rating (0-10 scale) and venous samples for lactate were obtained each minute. Lactate and ventilatory thresholds were derived from lactate and gas-exchange data. Blood pressure was obtained before exercise, 5 min postinfusion, at maximum exercise, and 5 min postexercise. There were no control-Pl differences. The naloxone trial demonstrated decreased exercise time (96% Pl; P Ͻ 0.01), total cumulative work (96% Pl; P Ͻ 0.002), peak V O2 (94% Pl; P Ͻ 0.02), and HR (96% Pl; P Ͻ 0.01). Other variables were unchanged. HR and V E were the same at the final common workload, but perceived exertion was higher (8.1 Ϯ 0.5 vs. 7.1 Ϯ 0.5) after naloxone than Pl (P Ͻ 0.01). The threshold for effort perception amplification occurred at ϳ60 Ϯ 4% of Pl peak V O2. Thus we conclude that peak work capacity was limited by perceived exertion, which can be attenuated by endogenous opioids rather than by physiological limits. peak oxygen consumption; lactate threshold; endogenous opioids; physiological fatigue THE DISCOMFORT ASSOCIATED with skeletal muscle activity and/or with increased breathing during exercise in healthy fit people may determine when the exercise is terminated (8, 9). Surbey et al. (22) have speculated that effort sensation, in turn, may be modulated by endogenous opioid release.The ventilatory component of discomfort is due, in part, to the disproportionate increase in minute ventilation (V E) relative to the increase in workload, which results from stimulation by H ϩ and CO 2 formed during buffering of lactic acid released during high levels of exercise (24, 25). The ventilatory threshold (VT) denotes the work rate at which this disproportionate increase occurs. Robertson (16) speculated that during high-intensity, continuous exercise above VT, discomfort becomes a limiting factor. This level of work has also been associated with endogenous opioid release (23). Endogenous opioids, in turn, have been shown to reduce V E (15, 27) for a given workload, thereby diminishing respiratory discomfort. Similarly, these endogenous opioids would also diminish discomfort originating from exercising muscles (18,19).Although a small number of investigations have assessed the role of opioid blockade on maximum exercise capacity (5,12,20,22), the effect in healthy subjects has not been thoroughly defined. To assess the possible impact of endogenous opioids on effort pe...