Sex differences in tolerance to morphine antinociception in intra-nucleus accumbens administration in rat

Sex differences in analgesic responses and tolerance to morphine under the systemic and injection in some nuclei of brain have been reported, although the trend of these differences varies across studies. The purpose of the present study was to determine whether development tolerance to the analgesic effect of morphine differs between male and female in intra-nucleus accumbens administration of morphine in rat. In order to induce tolerance, adult male and female rats were injected with morphine (2.5, 5, 10 and 50 μg/0.5 μL; intraaccumbal infusions) for 4 consecutive days during which, non-tolerant group received a single dose of morphine (saline for 3 consecutive days and morphine on 4th day) and control vehicle group received saline (4 consecutive days). On day 4, tail flick and hot-plate test was done for pain evaluation in separated groups. The results of the study revealed 4 effects. 1) No significant morphine antinociceptive effect by tail flick test in both sexes, while significant antinociceptive effect of morphine were observed in the hotplate test. 2) No significant sex differences were observed in hotplate test after acute morphine injection to animals. 3) Rats showed significantly tolerance to morphine analgesic effects under protocol by hotplate test. 4) Female rats showed significantly more tolerance to morphine analgesic effects than males by hotplate test. These data demonstrate that there were sex differences in tolerance to morphine antinociception in intra-nucleus accumbens administration that is dependent, in part, on the nociceptive test.