Authors: Stevens S Negus Nancy K Mello
Publish Date: 2001/10/12
Volume: 159, Issue: 3, Pages: 275-283
Abstract
Rationale Gonadal steroid hormones altered opioid antinociception under some conditions in rodents and we reported previously that chronic estradiol enhanced kappa but not mu opioid antinociception in ovariectomized rhesus monkeys Sex differences have also been observed in the antinociceptive effects of opioid agonists These findings suggest that gonadal hormones may modulate opioid antinociception Objectives To extend our previous studies of estradiol by examining the effects of progesterone alone estradiol in combination with progesterone and testosterone alone on opioid antinociception in ovariectomized rhesus monkeys Methods Opioid effects were studied during chronic treatment with vehicle sesame oil or with progesterone alone P 032 mg/kg per day a combination of progesterone+estradiol P+E 032 mg/kg per day P + 0002 mg/kg per day E or testosterone alone T 032 mg/kg per day Opioid antinociception in a warmwater tailwithdrawal procedure was examined with the selective kappa opioid agonist U50488 the selective mu agonist morphine and the two mixedaction opioids butorphanol and nalbuphine Results The steroid treatment regimens produced physiological levels of progesterone and estradiol similar to peak levels observed during the luteal phase of the menstrual cycle and physiological levels of testosterone similar to those observed in intact males Treatment with P P+E or T did not alter baseline thermal nociception P+E significantly increased the potency of U50488 at 50°C but not at 54°C Gonadal hormone treatments had little or no effect on antinociception produced by morphine butorphanol or nalbuphine at either temperature Conclusions These findings further suggest that chronic treatment with physiological levels of gonadal hormones may modulate the antinociceptive effects of U50488 in ovariectomized rhesus monkeys
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