DEVELOPMENTAL EXPRESSION OF THE MU-OPIOID, KAPPA-OPIOID, AND DELTA-OPIOID RECEPTOR MESSENGER-RNA 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 a ges. 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 recept or mRNA is first detected at E12.5 in several peripheral tissues, incl uding the olfactory epithelium, heart, limb bud, and tooth. in the bra in, both mu and kappa mRNAs are first detected at E11.5 in the basal g anglia and midbrain, respectively. During mid-gestation and late gesta tion, the expression of both mu and kappa receptors extends to other b rain 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 o f mu and kappa receptors already have been established. Compared with mu and kappa, delta receptor mRNA expression in the brain begins relat ively late, and the expression levels remain very low even at E19.5. I n 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 ear lier ages and suggest that early developmental events in both neural a nd non-neural tissues may be modulated by opioid receptors. Several ex amples 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.