INTERACTIONS AMONG AGING, GENDER, AND GONADECTOMY EFFECTS UPON MORPHINE ANTINOCICEPTION IN RATS

In addition to age-related deficits in morphine antinociception in fem ale rats, gender and gonadectomy differences have also been observed, with male rats displaying greater magnitudes of effects than females a nd castrated males. Since there are little data indicating how aging, gender, and gonadectomy interact in modulating morphine antinociceptio n, the present study evaluated alterations in this response as functio ns of age (6, 12, 18, and 24 months), gender, and gonadal status (inta ct, gonadectomized) across a dose range (1-10 mg/kg) and time course ( 0.5-2 h) on the tail-flick test. The maximal percentage effect (MPE) o f morphine (1 mg/kg) was significantly increased in castrated males (1 8 months), sham females (18 and 24 months), and ovariectomized females (18 months) relative to 6-month-old groups. Increases in the MPE of m orphine (1 mg/kg) occurred in sham females (24 months) relative to cor responding sham males and ovariectomized females' The MPE of morphine (2.5 mg/kg) was significantly increased in sham males (18 months) and decreased in sham females (12 months). Decreases in the MPE of morphin e (2.5 mg/kg) occurred in castrated males (18 and 24 months) as well a s sham (18 months) and ovariectomized (18 and 24 months) females relat ive to sham males. Whereas the MPE of morphine (5 mg/kg) was unchanged by these variables, the MPE of morphine (10 mg/kg) was significantly decreased in sham females (18 and 24 months) relative to females aged 6 months, as well as males and ovariectomized females aged 24 months. Age-related changes in morphine's dose-response curves varied as a fun ction of gender, with decreases in ED50 for sham males and increases i n ED50 for sham females, with ovariectomy eliminating the latter effec t. Thus, gender emerges as an important variable in assessing aging di fferences in morphine antinociception in rats, and it appears that cir culating gonadal hormones in females may account in part for these dif ferences.