GENDER-RELATED DIFFERENCES IN THE ANTINOCICEPTIVE PROPERTIES OF MORPHINE

As part of an effort to examine gender-related differences in the abus e liability of morphine, the present parametric study was undertaken t o systematically establish whether there are gender-related difference s in the antinociceptive activity of morphine in rats. Our results sho wed that male rats were uniformly more sensitive to the antinociceptiv e properties of morphine than were females in three different assays, i.e., the hot-plate, tail-flick and abdominal-constriction tests. This enhanced sensitivity to morphine was reflected in the peak antinocice ptive effect, the magnitude of antinociception (i.e., area under the t ime-action curve), the duration of the antinociceptive response and th e 50% effective dose. These differences appear to reflect markedly enh anced central nervous system sensitivity to morphine in males, compare d with females, because we observed no gender-linked differences in se rum levels of morphine after its injection, at the time when peak anti nociceptive effects were observed. Furthermore, these gender-related d ifferences appear to be reflected in antinociception thought to be med iated by both spinal and supraspinal mechanisms. Finally, our results suggest that the acute effects of steroids play little role in the gen der-related differences observed, because short-term castration did no t alter the gender-related differences we observed. Rather, it appears more probable that the organizational effects of steroids during crit ical periods in development, which determine gender-related distinctio ns, may be significant in the male-female differences we have observed . In view of a great deal of largely anecdotal data for humans that su ggest that there may be gender-related differences in the abuse liabil ity of psychoactive substances, the model described in this paper may provide a means to examine this important issue.