Developmental expression of mu and delta opioid receptors in the rat brainstem: evidence for a postnatal switch in mu isoform expression.

Opioid receptors are expressed in the brain during fetal and postnatal development, and the expression patterns vary with developmental age. To investigate the role of opioids in brain development, immunoblotting and immunohistochemical techniques were used to determine mu (MOR) and delta (DOR) opioid receptor expression levels and regional distributions in fetal, early postnatal and adult rat brainstem. Two immunoreactive bands were seen on Western blots of brainstem lysates for both MOR (50 and 70 kDa) and DOR (30 and 60 kDa). The expression levels of the isoforms changed dramatically between 6 and 15 days after birth. Total MOR protein was expressed at low levels in fetal and early postnatal animals with the 50-kDa band predominating. MOR expression then increased in the older animals and the 70-kDa isoform became dominant. Total DOR protein showed the opposite pattern, being high in the fetal and neonatal brainstem and low in the juvenile and adult. A postnatal switch in isoform expression for DOR was not evident in our study. In general, regional brainstem distributions in developing and adult animals were comparable to those reported in the literature, and both receptors were localized in the same areas where opioid receptor expression was high. It was concluded that MOR and DOR are developmentally regulated in the brainstem of the rat, that the isoform ratio switches postnatally from a fetal-neonatal pattern to a juvenile-adult pattern and that both receptors are generally expressed in the same brainstem regions from E16 to adult.