A comparison of morphine analgesic tolerance in male and female mice.

Studies comparing morphine tolerance in males and females are rare, and all studies to date have utilized the rat. To generalize from findings with rats morphine tolerance was investigated in male and female mice using the tail-withdrawal test. Three and 7 days of systemic morphine injections produced significant but unequal rightward shifts in the morphine dose-response curve such that females displayed greater increases in analgesic ED(50) values when compared to males. In a separate experiment, males and females displayed similar reductions in morphine analgesic sensitivity when %MPE (maximum possible effect) and %total (area under the curve) were compared after 3 days of morphine. Differences in initial morphine sensitivity between sexes were not observed in either study. The data demonstrate that, in contrast to rats, female mice undergo greater reductions in morphine analgesia relative to males following chronic morphine, but this sex difference may depend on the method of assessing analgesia. Furthermore, the duration and/or cumulative dose of morphine treatment does not affect the expression of sex differences in morphine tolerance.