Interactions of "ultra-low" doses of naltrexone and morphine in mature and young male and female rats

Sex and age influence morphine analgesia in humans and animals. Mature rats show greater morphine analgesia in males than in females. Ultra-low doses of naltrexone enhance morphine analgesia. In mature rats (18-22 weeks), naltrexone (0.002-2.0 mg/kg)-morphine (2 mg/kg) cotreatment enhanced morphine analgesia in females, an effect inversely related to naltrexone dose. Conversely, in mature male rats, naltrexone tended to decrease morphine analgesia with increasing dose. In young rats (8-10 weeks), morphine analgesia was unrelated to sex and in both sexes the naltrexone-morphine interaction was negligible. These data show that dose, age, and sex alter the naltrexone-morphine interaction in rats.