Sex differences in supraspinal morphine analgesia are dependent on genotype

Several variables have been reported to affect the expression of sex differ ences in the analgesic potency of morphine. Although the effect of genetic background on morphine analgesia has been well documented, the relevance of genotype to sex differences in morphine analgesia has rarely been consider ed. The present study investigated morphine dose-response relationships in male and female mice of 11 inbred mouse strains on the tail-withdrawal test after i.c.v. administration. Large differences in morphine analgesic poten cy were observed between strains, reflecting the important influence of gen otype on this trait. We identified three strains (AKR/J, C57BL/6J, and SWR/ J) in which males displayed approximately 3.5- to 7.0-fold greater sensitiv ities to the analgesic effects of morphine than did their female counterpar ts. In contrast, in the CBA/J strain, females were found to be approximatel y 5-fold more sensitive to morphine than were the males. In all other strai ns, morphine potency estimates between the sexes were not statistically dif ferent. These data support the importance of genotype, sex, and their inter action in the mediation of morphine analgesia and suggest that equivocal fi ndings regarding opioid sex differences in the literature may be partially accounted for by the use of different subject populations. The fact that fe male mice of the AKR/J and CBA/J strains exhibit 35-fold different morphine analgesic potency and that males of these strains are equally sensitive sh ould facilitate the mapping and identification of sex-specific genes of rel evance to morphine analgesia.