Role of steroids in sex differences in morphine-induced analgesia: activational and organizational effects.
The purpose of the present studies was to determine the role of either the organizational or activational sex steroids in mediating the sex differences observed in morphine-induced antinociception in the rat. To examine the organizational aspects, male pups were castrated at postnatal days 1 and 2; females were masculinized by large doses of testosterone on postnatal days 1 and 2. Adult male and female rats were also castrated over a period of 2 months to examine the role of the acute activational effects of the opiates in the already sexually differentiated adult rat brain. The results of these studies demonstrate that there were no alterations in the sex differences in opiate analgesia in castrated adult male and female rats; thus, male- and female-specific responses to opiate-induced antinociception were maintained even in the absence of the acute membrane-mediated effects of sex steroids. On the other hand, in male rats, castrated at postnatal days 1 and 2, the morphine dose-response curve shifted markedly to the right and, in fact, was almost identical to that observed in untreated females. Conversely, in female rats, masculinized by large doses of testosterone early in prenatal life, the morphine dose-response curve shifted to the left, yielding a dose-response curve that resembled that in normal males. These results strongly suggest that the sex differences that have been observed in morphine-induced analgesia are due to the organizational effects of sex steroids in the developing rat brain, rather than their acute activational effects in adulthood.
Cicero
Theodore J
TJ
Washington University School of Medicine, Department of Psychiatry, St. Louis, Missouri 63110, USA. cicerot@msnotes.wustl.edu
Nock
Bruce
B
O'Connor
Lynn
L
Meyer
Edward R
ER
D000465:Algorithms; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009919:Orchiectomy; D010052:Ovariectomy; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D013256:Steroids / Q000502:physiology*; D013739:Testosterone / Q000494:pharmacology
D000701:Analgesics, Opioid; D012739:Gonadal Steroid Hormones; D013256:Steroids; D013739:Testosterone; D009020:Morphine