Gender-related differences exist in cortical [3H]nisoxetine binding and are not affected by prenatal morphine...

The present study was designed to test the hypothesis that prenatal morphine, which differentially affects hypothalamic norepinephrine content and turnover in male and female rats, has sexually dimorphic effects on the density of hypothalamic norepinephrine uptake sites in adult offspring. The binding characteristics of norepinephrine transporters were examined in the hypothalamus, preoptic area and frontal cortex of adult male and female rats exposed to morphine (5-10 mg/kg, twice daily) or saline on gestation days 11-18. There was a gender-related difference in the density of norepinephrine uptake sites measured by [3H]nisoxetine binding in the frontal cortex of saline controls, with control males having significantly fewer binding sites than control females. Prenatal morphine administration did not reverse or eliminate this difference. Additionally, prenatal morphine exposure had no effects on either the binding capacity or the affinity of norepinephrine uptake sites in the hypothalamus, preoptic area or frontal cortex of adult progeny. Thus, alterations in hypothalamic norepinephrine content and turnover following prenatal morphine exposure are not reflected in alterations in norepinephrine uptake sites. However, recent immunocytochemical work in our laboratory correlated reductions in hypothalamic norepinephrine content and turnover rate with reductions in tyrosine hydroxylase and dopamine-beta-hydroxylase fiber density in the hypothalamus of morphine-exposed female rats. Therefore, the present results may suggest that compensatory mechanisms increase the density of norepinephrine uptake sites in hypothalamic terminal fields of morphine-exposed females.