Prevention by naltrexone of tolerance to the rate-decreasing effects of morphine on schedule-controlled responding in the pigeon.

Abstract

Key-pecking in the pigeon was maintained under 10-min fixed-interval and 30-response fixed-ratio schedules of food presentation. Naltrexone alone (0.003–17 mg/kg) had no systematic effect on responding at any dose studied, and 10 and 17 mg/kg morphine practically eliminated responding. When naltrexone regularly preceded daily injections of morphine, tolerance was prevented for some dose combinations but not for others. If the daily dose of morphine was 17 mg/kg, tolerance was prevented by 1.0 mg/kg naltrexone but not by 0.3 mg/kg naltrexone. If the dose of naltrexone was 0.56 mg/kg, tolerance was prevented for 10 mg/kg morphine but not for 17 mg/kg morphine. Thus naltrexone prevented the development of tolerance to the rate-decreasing effects of morphine, although there were doses of naltrexone which completely antagonized the acute effects of morphine but which did not prevent tolerance development. The relative doses of naltrexone and morphine, not the absolute doses, determined whether or not development of tolerance was prevented. When combinations of naltrexone (0.3 or 1.0 mg/kg) and morphine (17 mg/kg) preceded experimental sessions by 6 h, the effects of the combination with 0.3 mg/kg naltrexone were more like those of 17 mg/kg morphine alone, whereas the effects of the combination with 1.0 mg/kg naltrexone were almost indistinguishable from those of saline. Differences in prevention of tolerance by doses of naltrexone that antagonized the acute effects of morphine were probably due to differences in duration of effect.