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Previous research shows that low to moderate doses of opiate antagonists do not affect running whereas high doses decrease running. This decrease in running has been interpreted as a motivational effect; however, it may also be an effect of motoric impairment, malaise, or sedation. The purpose of the present study was to evaluate the effects of high doses of naltrexone on running and responding for the opportunity to run in rats. Seven male Wistar rats, trained to press levers for the opportunity to run for 30 s, were exposed to a series of tandem fixed-ratio 1 variable-interval (VI) schedules of reinforcement where the value of the VI schedule was varied. Four rats were exposed to a VI 60-, VI 30-, and VI 5-s schedule order and the remaining three were exposed to VI 5-, VI 30-, and VI 60-s schedule order. After 50 sessions, doses of 10, 20, or 40 mg/kg of naltrexone were administered prior to a session. Results showed that naltrexone significantly decreased rates of lever pressing and running and increased postreinforcement latency to respond. Within-session analyses showed that naltrexone significantly decreased responding and running during the first schedule of a session regardless of schedule value. The lack of interaction of the drug effect with the schedule of reinforcement is inconsistent with a motivational effect. Consequently, it was concluded that decreases in running caused by high doses of naltrexone are not motivational and should not be taken as evidence in support of the opiate hypothesis.