Postnatal development of multiple opioid receptors in rat brain.

Recent studies have demonstrated that opioid receptors may be functional at early stages of ontogeny, and may modulate specific developmental functions. It is presently unknown, however, which particular opioid receptor subtype(s) may be involved. In the pre-ent study, we have used selective radioligand binding conditions in combination with quantitative autoradiography to examine the ontogeny of mu-, kappa- and delta-opioid receptors in the developing rat brain. Membrane binding data indicate that the affinities of mu-, kappa- and delta-sites for radiolabeled drugs are similar in neonatal and adult rats. mu- And kappa-receptors are present in significant densities during early neonatal periods, while delta-receptors appear much later. Autoradiographic data indicate that mu- and kappa-receptors appear early in the development of several brain regions, including the neostriatum, olfactory tubercle and rostral midbrain, and later in other regions such as the thalamus and hypothalamus. Whereas the densities of kappa-binding sites remain relatively constant throughout development, there is a transient appearance and/or redistribution of mu-receptors in several brain areas. delta-Receptors are present in low densities in the basal forebrain at birth. The level of delta-receptor binding increases markedly during the third postnatal week in all brain areas examined. The early appearance of mu- and kappa-receptors during the ontogeny of the brain suggests that these receptors, at least in part, mediate the developmental actions of exogenous and endogenous opioids.