Developmental Expression of the μ, κ, and δ Opioid Receptor mRNAs in Mouse

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Abstract
To characterize further the establishment of the opioid system during prenatal mouse development, we have examined the spatial and temporal expression patterns of μ, κ, and δ opioid receptor mRNAs and find that the expression patterns of these mRNAs are distinct at all ages. Within the embryo, κ 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, μ receptor expression is first detected in the facial–vestibulocochlear preganglion complex, whereas δ 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 μ and κ mRNAs are first detected at E11.5 in the basal ganglia and midbrain, respectively. During mid-gestation and late gestation, the expression of both μ and κ receptors extends to other brain regions that exhibit high expression in the adult, including the medial habenula, hypothalamus, pons, and medulla for μ and the basal ganglia, thalamus, hypothalamus, raphe, and ventral tegmental area for κ. Thus by E17.5, many aspects of the adult expression patterns of μ and κ receptors already have been established. Compared with μ and κ, δ 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, δ 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. μ 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.