Alterations of prenatal morphine exposure in mu-opioid receptor density in hypothalamic nuclei associated with sexual behavior.

Our previous work demonstrated that prenatal morphine exposure twice daily during gestational days 11-18 differentially alters male and female sexual behavior. One possible explanation may be that prenatal morphine exposure alters the sexual behavior via alterations of mu-opioid receptors in brain regions involved in reproductive function and behavior, including the ventromedial nucleus of the hypothalamus (VMH), arcuate nucleus (ARC), and medial preoptic area (mPOA). In experiment 1, mu-opioid receptor density was analyzed in three groups of adult male rats: gonadally intact, gonadectomized (GNX), and GNX and testosterone 17beta-propionate-treated (TP). In experiment 2, mu-opioid receptor density was analyzed in four groups of adult female rats: ovariectomized (OVX), OVX and estradiol benzoate-treated (EB), OVX and progesterone-treated (P), and OVX and EB- and P-treated (EB+P). Experiment 1 demonstrated that prenatal morphine exposure lowered the mu-opioid receptor density in the mPOA of adult, gonadally intact and in TP males, while this difference was not apparent in GNX male rats. Experiment 2 demonstrated that prenatal morphine exposure increased mu-opioid receptor density in OVX females, while decreasing it in EB females in the VMH. When compared to our previous sexual behavior data, the present results demonstrate that at least some changes in sexual behavior of adult male and female rats prenatally exposed to morphine may be related to alterations in mu-opioid receptors in brain regions controlling sexual behavior.