Organizational manipulation of gonadal hormones and systemic morphine analgesia in female rats: Effects of adult ovariectomy and estradiol replacement

Previous research has indicated the importance of sex in mediating the larger magnitude of p-opioid receptor agonist-induced analgesia in male relative to female rodents. Whereas manipulations involving the adult activational effects of gonadal hormones minimally alter these analgesic sex differences, manipulations involving neonatal organizational effects of gonadal hormones have previously been shown to profoundly affect morphine analgesia. Thus, adult male rats neonatally castrated oil the first day after birth displayed reductions in morphine analgesia relative to sham-operated males, and adult female rats neonatally treated with testosterone propionate on the first day after birth displayed enhancements in morphine analgesia relative to vehicle-treated females. Because neonatal androgenization in female rats produces an anovulatory syndrome that could change their adult hormonal milieu, the present study examined whether adult ovariectomy altered the magnitude of systemic morphine analgesia (1-5 mg/kg) in neonatal androgenized female rats relative to neonatal vehicle-treated female rats as well as gonadal steroid hormone replacement with estradiol benzoate. Intact male rats displayed significantly greater magnitudes and potencies (2- to 2.3-fold leftward shift) of systemic morphine analgesia than female rats treated neonatally with either vehicle (1-5 mg/kg) or testosterone (1.7-5 mg/kg). In turn, neonatal androgenized female rats displayed significantly greater magnitudes of systemic morphine (1, 5 mg/k) analgesia than vehicle-treated female rats accompanied by a smaller 20% leftward shift in potency. Adult ovariectomy minimally affected morphine analgesia in neonatal vehicle-treated females, while significantly reducing the magnitude (1 mg/kg), but not the potency of morphine analgesia in neonatal androgenized female rats. Estradiol replacement therapy significantly increased the magnitude of morphine analgesia in both groups at some doses, but only changed the potency (20-30%) in females treated neonatally with vehicle. Taken together, these data A suggest a limited organizational-activational gonadal hormone interaction in the mediation of systemic morphine analgesia in female rats. (c) 2005 Elsevier B.V All rights reserved.