Morphine tolerance after chronic intracerebroventricular injection in male and female mice.

We compared morphine analgesia ED(50) values of male and female mice prior to (Day 1) and after (Day 4) 3 days of intracerebroventricular morphine injections. Increases in ED(50) values from Day 1 to Day 4, indicating tolerance, were of similar magnitude in both sexes. The data suggest that spinal opioid analgesic mechanisms, acting alone or in synergy with supraspinal loci, may contribute to pharmacodynamic explanations of sex differences in systemic morphine tolerance.