Effects of gonadal steroid hormone treatments on opioid antinociception in ovariectomized rhesus monkeys.
BACKGROUND
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.


OBJECTIVE
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; 0.32 mg/kg per day), a combination of progesterone+estradiol (P+E; 0.32 mg/kg per day P + 0.002 mg/kg per day E), or testosterone alone (T; 0.32 mg/kg per day). Opioid antinociception in a warm-water tail-withdrawal procedure was examined with the selective kappa opioid agonist U50,488, the selective mu agonist morphine, and the two mixed-action 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 U50,488 at 50 degrees C but not at 54 degrees 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 U50,488 in ovariectomized rhesus monkeys.
Negus
Stevens S
SS
Alcohol and Drug Abuse Research Center, Harvard Medical School, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA. negus@mclean.harvard.edu
Mello
Nancy K
NK
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002077:Butorphanol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000097:blood / Q000494:pharmacology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood / Q000494:pharmacology*; D008253:Macaca mulatta; D009266:Nalbuphine / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010052:Ovariectomy; D010147:Pain Measurement / Q000187:drug effects*; D011374:Progesterone / Q000097:blood / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000502:physiology; D013739:Testosterone / Q000097:blood / Q000494:pharmacology
D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D012739:Gonadal Steroid Hormones; D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009266:Nalbuphine; D002077:Butorphanol