V-411

Naltrexone-HCl (I-HCl) [16676-29-2] alone (0.003-17 mg/kg) had no systematic effect on responding at any dose studied, and 10 and 17 mg/kg morphine sulfate (II sulfate) [64-31-3] practically eliminated responding in pigeons maintained on key-pecking under 10-min fixed-interval and 30-response fixed-ratio schedules of food presentation.When I regularly preceded daily injections of II, tolerance was prevented for some dose combinations but not for others.If the daily dose of II was 17 mg/kg, tolerance was prevented by 1.0 mg/kg I but not by 0.3 mg/kg I.If the dose of I was 0.56 mg/kg, tolerance was prevented for 10 mg/kg II but not for 17 mg/kg II.Thus, I prevented the development of tolerance to the rate-decreasing effects of II, although there were doses of I which completely antagonized the acute effects of II but which did not prevent tolerance development.The relative doses of I and II, not the absolute doses, determined whether or not development of tolerance was prevented.When combinations of I (0.3 or 1.0 mg/kg) and II (17 mg/kg) preceded exptl. sessions by 6 h, the effects of the combination with 0.3 mg/kg I were more like those of 17 mg/kg II alone, whereas the effects of the combination with 1.0 mg/kg I were almost indistinguishable from those of saline.Differences in prevention of tolerance by doses of I that antagonized the acute effects of II were probably due to differences in duration of effect.