Ontogeny of μ-, δ- and κ-opioid receptors mediating inhibition of neurotransmitter release and adenylate cyclase activity in rat brain

Taco J. De Vries, François Hogenboom, Arie H. Mulder, Anton N M Schoffelmeer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)63-69
Number of pages7
Issue number1
Publication statusPublished - 1 Jun 1990

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