Interaction of β-casomorphins with multiple opioid receptors: In vitro and in vivo studies in the newborn rat brain

β-Casomorphins (β-CMs) are peptidic fragments of bovine β-casein with potent opioid activity. In view of a possible physiological meaning of these milk-derived compounds, we have studied the affinity of some natural β-CMs and some semisynthetic analogues for μ-, δ- and κ-brain opioid receptors in newborn and adult rat. Moreover we have investigated whether a chronic treatment with the potent analogue d-Ala2-β-CM-4-NH2 during the suckling period could affect μ and δ opioid receptor function. Our findings demonstrate that β-CMs are μ-oriented compounds both in adult and in newborn rat brain. They display the same μ-affinity in newborn as well as in adult animals, however δ and κ-affinities appear different, probably due to the lower degree of maturation of these two receptors in the first days of life. A prolonged treatment with d-Ala2-β-CM-4-NH2 during the preweanling period is able to induce a delay in the ontogenetic increase of δ-receptor affinity, whereas it affects neither the affinity nor the density of μ-receptors. This effect could be related to a general action of opioids on cerebral maturative processes; moreover we point out that a β-CMs analogue, given orally to newborn animals, can induce modifications at central level, suggesting thus the hypothesis that β-CMs could be a biologically active peptide in the first stages of life. © 1986 Elsevier Science Publishers B.V. (Biomedical Division) All rights reserved.