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Vol. 289, Issue 3, 1370-1375, June 1999
The College of Staten Island/City University of New York and
College of Staten Island/Institute for Basic Research Center for
Developmental Neuroscience, Staten Island, New York (B.K.); and
Department of Psychology and Program in Neuroscience, University of
Illinois at Urbana-Champaign, Champaign, Illinois (S.G.W., J.S.M.)
Several variables have been reported to affect the expression of sex
differences 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 considered. 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 potency were observed between
strains, reflecting the important influence of genotype 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 sensitivities to the
analgesic effects of morphine than did their female counterparts. In
contrast, in the CBA/J strain, females were found to be approximately
5-fold more sensitive to morphine than were the males. In all other
strains, morphine potency estimates between the sexes were not
statistically different. These data support the importance of genotype,
sex, and their interaction in the mediation of morphine analgesia and suggest that equivocal findings regarding opioid sex differences in the
literature may be partially accounted for by the use of different
subject populations. The fact that female 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 should facilitate the
mapping and identification of sex-specific genes of relevance to
morphine analgesia.
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