Ontogenetic studies on MU, delta and kappa opioid receptors in rat brain

The ontogenetic pattern of multiple opioid binding sites in rat brain from birth until weaning has been investigated. [3H]-dihydromorphine ([3H]-DHM)3 [3H]-D-Ala2-D-Leu5-enkephalin ([3H]-DADLE) and [3H]-dynorphin A (1-8) ([3H]-DYN) as markers of mu (μ), delta (δ) and Kappa (K) sites were utilized respectively. The analysis of the kinetic parameters of [3H]-DHM binding shows that, at birth, μ sites possess an affinity similar to that of adult animals, and a density of 50%, which reaches 80% of the adult value at day 4. On the contrary, [3H]-DADLE binding in the first post-natal days shows low affinity and low density and δ-sites do not reach values comparable to the adult ones until the second week of life. The kinetic parameters of [3H]-DYN binding are almost undetectable during the preweanling period, due to the very low density of K sites at this stage of life. Displacement studies with μ-, δ- and K-selective ligands show that the Ki values on [3H]-DHM binding sites were similar in 4 day old and adult animals for all the tested compounds, whereas Ki values on [3H]-DADLE and [3H]-DYN binding sites reflected an immaturity of δ and K receptors. In conclusion, our data suggest that multiple opioid receptors follow different ontogenetic patterns. In the first stages of life only μ receptors are almost mature and possibly mediate endogenous opioid actions and exogenous opiate pharmaco-toxicological effects. © 1986.