NALTREXONE ANTAGONIZES THE ANALGESIC AND IMMUNOSUPPRESSIVE EFFECTS OFMORPHINE IN MICE

A study was undertaken to investigate the relationship between morphin e-induced analgesia and immunosuppression after acute administration. In male CD1 mice, morphine (10.0-100.0 mg/kg s.c.) produced a U-shaped immunosuppressive dose-effect curve on splenic natural killer (NK) ac tivity. Morphine also induced dose-related analgesia, as measured by a n increase in tail-flick latency during thermal application; these ana lgesic effects were antagonized by naltrexone (1.0-10.0 mg/kg). In add ition, morphine-induced suppression of splenic NK activity was antagon ized in a dose-dependent manner and, at one dose of naltrexone (10.0 m g/kg), splenic NK activity was augmented. To investigate further the r elationship between naltrexone antagonism of morphine-induced analgesi a and immunomodulation, single doses of morphine (10.0-100.0 mg/kg) we re administered to mice pretreated with naltrexone (0.01-10.0 mg/kg) o r saline. A dose of 10.0 mg/kg of morphine produced 35% of the maximal possible effect in the analgesia study and no immunosuppression, wher eas a dose of 32.0 mg/kg produced a maximal analgesic effect and signi ficant suppression of NK activity. Naltrexone blocked morphine-induced analgesia and immunosuppression in a dose-dependent fashion. Moreover , the combination of 1.0 mg/kg of naltrexone and 32.0 mg/kg of morphin e elevated splenic NK activity. A large dose of morphine (100.0 mg/kg) elicited full analgesia and had no effect on splenic NK activity in s aline- or naltrexone-pretreated mice. Collectively, these results supp ort the view that, in mice, morphine-induced analgesia and immunosuppr ession are mediated through a common opioid receptor type.