Developmental expression of the mu, kappa, and delta opioid receptor mRNAs in mouse.

To characterize further the establishment of the opioid system during prenatal mouse development, we have examined the spatial and temporal expression patterns of mu, kappa, and delta opioid receptor mRNAs and find that the expression patterns of these mRNAs are distinct at all ages. Within the embryo, kappa is the first opioid receptor expressed, with transcripts detected in the gut epithelium as early as embryonic day 9.5 (E9.5). By E10.5, mu receptor expression is first detected in the facial-vestibulocochlear preganglion complex, whereas delta receptor mRNA is first detected at E12.5 in several peripheral tissues, including the olfactory epithelium, heart, limb bud, and tooth. In the brain, both mu and kappa mRNAs are first detected at E11.5 in the basal ganglia and midbrain, respectively. During mid-gestation and late gestation, the expression of both mu and kappa receptors extends to other brain regions that exhibit high expression in the adult, including the medial habenula, hypothalamus, pons, and medulla for mu and the basal ganglia, thalamus, hypothalamus, raphe, and ventral tegmental area for kappa. Thus by E17.5, many aspects of the adult expression patterns of mu and kappa receptors already have been established. Compared with mu and kappa, delta receptor mRNA expression in the brain begins relatively late, and the expression levels remain very low even at E19.5. In contrast to its late appearance in the brain, however, delta is the first opioid receptor expressed in the dorsal root ganglion, at E12.5, before its expression in the spinal cord begins at E15.5. Mu receptor is the first opioid receptor expressed in the spinal cord, at E11.5. These results extend previous ligand-binding data to significantly earlier ages and suggest that early developmental events in both neural and non-neural tissues may be modulated by opioid receptors. Several examples of possible autocrine and paracrine loops of opioid peptide and receptor expression have been identified, suggesting a role for these local circuits in developmental processes.