EFFECTS OF PRENATAL MORPHINE AND ADULT ESTROGEN ADMINISTRATION ON MU-OPIOID INHIBITION OF NOREPINEPHRINE RELEASE FROM HYPOTHALAMIC SLICES

The present study tested the hypotheses that exposure to morphine in u tero (10 mg/kg twice a day on gestation days 11-18) and acute estrogen treatment in adulthood alter mu-opioid regulation of hypothalamic nor epinephrine (NE) release in sexually mature rats. Both basal and KCl-s timulated NE releases were measured in superfused hypothalamic and pre optic area (POA) slices preloaded with H-3-NE. The mu-opioid receptor agonist D-Ala(2), MePhe(4)-Gly-ol(5)-enkephalin (DAMGO; 10 or 100 nM) or the opioid antagonist naloxone (1 mu M) was applied to some slices 15 min prior to KCl stimulation. Prenatal morphine had no effect on ba sal or KCl-stimulated release of preloaded H-3-NE from hypothalamic an d POA slices from adult male progeny. Neither the mu-opioid agonist DA MGO nor the nonspecific antagonist naloxone significantly affected KCl -evoked overflow of H-3-NE in slices from either brain region of male rats. Adult female offspring were ovariectomized (OVX), and some were injected with a replacement dose of estrogen 48 h prior to sacrifice. Prenatal morphine had no effect on basal or KCl-stimulated release of H-3-NE from hypothalamic or POA slices or on the response of slices to opioid drugs. Estrogen treatment modestly increased KCl-evoked releas e of H-3-NE from POA slices from females. Moreover, there was a signif icant interaction between opioid drugs and estrogen treatment on KCl-e voked overflow of H-3-NE. In hypothalamic and POA slices from OVX fema les, DAMGO reduced KCl-evoked efflux of H-3-NE. This inhibitory effect of DAMGO was not apparent in slices from estrogen-treated females. In addition, naloxone increased KCl-stimulated NE release in slices from both hypothalamus and POA of estrogen-treated female rats but not con trol OVX females. Thus, prenatal exposure to morphine does not alter b asal, KCl-evoked or mu-opioid modulation of NE efflux from hypothalami c or POA slices in adult progeny of either sex. However, treatment of adult, OVX females with estrogen attenuates mu-opioid inhibition and p romotes the appearance of naloxone facilitation of KCl-evoked H-3-NE r elease from hypothalamic and POA slices.