Naltrexone antagonizes the analgesic and immunosuppressive effects of morphine in mice.
A study was undertaken to investigate the relationship between morphine-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) activity. Morphine also induced dose-related analgesia, as measured by an increase in tail-flick latency during thermal application; these analgesic effects were antagonized by naltrexone (1.0-10.0 mg/kg). In addition, morphine-induced suppression of splenic NK activity was antagonized in a dose-dependent manner and, at one dose of naltrexone (10.0 mg/kg), splenic NK activity was augmented. To investigate further the relationship between naltrexone antagonism of morphine-induced analgesia and immunomodulation, single doses of morphine (10.0-100.0 mg/kg) were administered to mice pretreated with naltrexone (0.01-10.0 mg/kg) or saline. A dose of 10.0 mg/kg of morphine produced 35% of the maximal possible effect in the analgesia study and no immunosuppression, whereas a dose of 32.0 mg/kg produced a maximal analgesic effect and significant 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 morphine 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 saline- or naltrexone-pretreated mice. Collectively, these results support the view that, in mice, morphine-induced analgesia and immunosuppression are mediated through a common opioid receptor type.
Carr
D J
DJ
Department of Pharmacology, LSU Medical Center, New Orleans.
Gerak
L R
LR
France
C P
CP
D000818:Animals; D004305:Dose-Response Relationship, Drug; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors*; D009271:Naltrexone / Q000494:pharmacology*; D010147:Pain Measurement; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D014407:Tumor Cells, Cultured
D007166:Immunosuppressive Agents; D009271:Naltrexone; D009020:Morphine