ONTOGENY OF MU-OPIOID, DELTA-OPIOID AND KAPPA-OPIOID RECEPTORS MEDIATING INHIBITION OF NEUROTRANSMITTER RELEASE AND ADENYLATE-CYCLASE ACTIVITY IN RAT-BRAIN

The ontogeny was examined of functional opioid receptors mediating presynaptic inhibition of neurotransmitter release and inhibition of dopamine (DA)-sensitive adenylate cyclase in the rat brain, using highly selective agonists for μ-, δ- and κ-receptors. On gestational day 17 (E17) strong inhibitory effects of the selective μ-agonist DAGO on the electrically evoked release of [3H]noradrenaline from cortical slices and of the selective κ-agonist U-50,488 on the electrically evoked release of [3H]DA from striatal slices were found. Electrically evoked release of [3H]acetylcholine from striatal slices was not detectable before postnatal day 7 (P7), but on that day it was already strongly inhibited by the selective δ-agonist DPDPE. Although μ- and δ-opioid receptors coupled to DA-sensitive adenylate cyclase in the striatum are likely to be physically associated in an opioid receptor complex in the adult, they were found to develop asynchronously. Whereas selective activation of μ-receptors with DAGO resulted in an inhibition of D1 dopamine receptor-stimulated adenylate cyclase activity on E17, activation of δ-receptors with DPDPE was not effective until P14. This study confirms the early appearance of μ- and κ-opioid receptors and the relatively late development of δ-opioid receptors in the rat brain. Most importantly, it shows that in an early stage of development opioids are already able to mediate modulation of noradrenergic (via activation of μ-receptors) and dopaminergic (via activation of μ- and κ-receptors) neurotransmission processes. Therefore, these opioid receptor types could play a role in brain development and/or developmental disturbances. © 1990.