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Vol. 290, Issue 3, 1132-1140, September 1999
Alcohol and Drug Abuse Research Center, Harvard Medical
School-McLean Hospital, Belmont, Massachusetts
Baseline nociception and opioid antinociception were compared in male
and ovariectomized female rhesus monkeys. Females were studied without
estradiol replacement or during treatment with estradiol
benzoate at doses (0.002 and 0.01 mg/kg/day) designed to mimic
17
-estradiol blood levels observed during different phases of the
menstrual cycle and during pregnancy. Baseline sensitivity to thermal
stimuli (42-54°C) was similar in male and ovariectomized female
monkeys. The antinociceptive effects of the µ-opioid agonists fentanyl, morphine, butorphanol, and nalbuphine were examined at 50 and
54°C. There were no sex-related differences in the antinociceptive effects of the high-efficacy µ agonist fentanyl; however, the lower-efficacy µ agonists morphine, butorphanol, and nalbuphine produced greater antinociceptive effects in males than in untreated ovariectomized females. Because butorphanol and nalbuphine have low
selectivity for µ versus 
receptors and may produce -agonist effects under some conditions, the high-efficacy, -selective agonist
U50,488 was also studied. U50,488 also produced greater antinociceptive
effects in males. Treatment with estradiol benzoate tended to enhance
opioid antinociception in the ovariectomized females; however, this
effect was significant only for butorphanol and U50,488 during
treatment with the highest dose of estradiol benzoate. These findings
suggest that opioid agonists usually produce greater antinociception in
male monkeys than in females, and the magnitude of these sex-related
differences may be inversely related to efficacy at µ receptors or
selectivity for µ versus receptors. Estradiol appears to have
little effect on µ-agonist antinociception in primates but may
enhance the antinociceptive effects of agonists.
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