Characterization of opioid receptor binding in adult and fetal sheep brain regions

Opioid receptor binding was studied in 3 brain regions from maternal and fetal sheep at various gestational ages. [3H]dihydromorphine [( 3H]DHM) and [3H]D-Ala2,D-Leu5-enkephalin ([3H]DADLE) were employed as radioligands to characterize mu- and delta-opioid receptor binding sites, respectively. [3H]DHM binding was found to be highest in maternal cerebellum, intermediate in frontal cortex, and lowest in hippocampus. [3H]DADLE binding was highest in frontal cortex, intermediate in hippocampus and lowest in cerebellum. Cerebellum was the only tissue studied which contained more [3H]DHM than [3H]DADLE binding sites. Dissociation constants for [3H]DHM binding were similar in all 3 brain regions from both maternal and fetal sheep, while the dissociation constant for [3H]DADLE binding was significantly higher in cerebellum than in frontal cortex or hippocampus. Binding of both mu- and delta-receptor-selective ligands was 70% of maternal values in fetal cerebellum at 97-101 days of gestation and gradually increased over the remainder of the gestational period studied. Levels of [3H]DHM binding in frontal cortex and hippocampus were also similar to maternal levels at all timepoints studied. In contrast, [3H]DADLE binding was only 40-45% of maternal levels in fetal frontal cortex and hippocampus prior to 110 days of gestation, followed by a rapid increase in binding in both brain regions.