Interactions among aging, gender, and gonadectomy effects upon morphine antinociception in rats

Abstract

In addition to age-related deficits in morphine antinociception in female rats, gender and gonadectomy differences have also been observed,with male rats displaying greater magnitudes of effects than females and castrated males. Since there are little data indicating how aging, gender, and gonadectomy interact in modulating morphine antinociception, the present study evaluated alterations in this response as functions of age (6, 12, 18, and 24 months), gender, and gonadal status (intact, 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) of morphine (1 mg/kg) was significantly increased in castrated males (18 months), sham females (18 and 24 months), and ovariectomized females (18 months) relative to 6-month-old groups. Increases in the MPE of morphine (1 mg/kg) occurred in sham females (24 months) relative to corresponding 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 morphine (2.5 mg/kg) occurred in castrated males (18 and 24 months) as well as sham (18 months) and ovariectomized (18 and 24 months) females relative 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 function of gender, with decreases in ED 50 for sham males and increases in ED 50 for sham females, with ovariectomy eliminating the latter effect. Thus, gender emerges as an important variable in assessing aging differences in morphine antinociception in rats, and it appears that circulating gonadal hormones in females may account in part for these differences.