Expression of opioid peptides and receptors in striatum and substantia nigra during rat brain development

We have used highly sensitive in situ hybridization to determine opioid receptor and peptide expression in embryonic and postnatal rat striatum, to follow the compartmentalization into patch and matrix structures, and have examined their developmental expression in the dopaminergic cell group of the substantia nigra (SN). Furthermore, opioid receptor binding sites were characterized in adjacent sections using highly selective ligands for the opioid receptor subtypes. The major findings of the study are: (1) striatal patches were first delineated by prodynorphin mRNA followed by mu opioid receptor mRNA expression at embryonic days 19 and 21, respectively; (2) in neonates, prodynorphin, mu and kappa opioid receptor mRNAs were transiently co-distributed within patches; (3) prodynorphin mRNA was co-expressed with mu but not kappa, receptor mRNA in neonatal patch neurons; (4) in the SN, kappa receptor and prodynorphin mRNAs were detected as early as embryonic days 15 and 19, respectively; (5) kappa receptor, but not prodynorphin, mRNA was expressed in dopaminergic neurons in the SN. The anatomical results are in agreement with the hypothesis that the endogenous opioid system has a trophic role during the development of striatal patch and matrix compartments and suggest the early regulation of dopamine release by kappa opioid receptors.