Prenatal exposure to morphine differentially alters gonadal hormone regulation of delta-opioid receptor binding in male and female rats

The present study tested the hypothesis that exposure to morphine on gestat ion days 11-18 differentially alters delta -opioid receptors in the brain o f adult male and female rats. In Experiment 1, the binding characteristics of delta -opioid receptors were examined in membrane homogenates from six b rain regions, including the hypothalamus (HYP), preoptic area, frontal cort ex (CX), ventral tegmental area, striatum (STR) and cerebellum of adult mal e and female rats. In Experiment 2, the density of delta -opioid receptors was assessed in the CX and STR using receptor autoradiography. Prenatal mor phine exposure has no effects on delta -opioid receptors in the brain of go nadally intact, adult male rats regardless of methodology. However, when ma le rats were gonadectomized in Experiment 2, morphine-exposed males have fe wer delta -opioid receptors than controls in the CX but not in the STR. The se reductions in cortical delta -opioid receptors are restored by testoster one replacement, demonstrating that prenatal morphine exposure alters testo sterone regulation in the CX of male rats. In ovariectomized (OVX) female r ats, prenatal morphine exposure increases the density of delta -opioid rece ptors in the frontal CX. Interestingly, this up-regulation of delta -opioid receptors is not present when the CX is investigated by autoradiography. M oreover, progesterone given alone or in combination with estrogen reduces t he density of delta -opioid receptors in the CX and STR of both saline- and morphine-exposed, OVX females. Thus, mid to late gestational morphine expo sure differentially alters the influence of adult gonadal hormones on delta -opioid receptors in the CX, decreasing the sensitivity in females and inc reasing it in males. This is also the first report to demonstrate that gona dal hormones regulate delta receptor densities in brain regions other than the HYP of OVX females. (C) 2001 Elsevier Science Inc.