Nociceptin/orphanin FQ knockout mice display up-regulation of the opioid receptor-like 1 receptor and alterations in opioid receptor expression in the brain

S. Clarke, Z. Chen, M. S. Hsu, R. G. Hill, J. E. Pintar, I. Kitchen

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

The opioid receptor-like 1 receptor is a novel member of the opioid receptor family and its endogenous peptide ligand has been termed nociceptin and orphanin FQ. Activation of the opioid receptor-like 1 receptor by nociceptin/orphanin FQ in vivo produces hyperalgesia when this peptide is given supraspinally but analgesia at the spinal level. Nociceptin/orphanin FQ also reverses stress-induced analgesia, suggesting that the peptide has anti-opioid properties. Nociceptin/orphanin FQ knockout mice show alterations in pain sensitivity and stress responses and display increased morphine dependence, suggesting an interaction of the nociceptin/orphanin FQ system with classical opioid receptor function. To determine if the behavioural phenotype of nociceptin/orphanin FQ knockout mice reflects changes in either opioid receptor-like 1 or classical opioid receptor expression, we have carried out quantitative autoradiography of the opioid receptor-like 1, μ-, δ- and κ-opioid receptors in the brains of these animals. Receptor density was measured on coronal sections from wild-type, heterozygous and homozygous mice using [3H]nociceptin, [3H][D-Ala2-N-methyl-Phe4-Gly5 ol] enkephalin, [3H]deltorphin-I, or [3H](-)-N-methyl-N-[7-(1-pyrrodinyl)-1-oxospiro[4,5]dec-8-yl]-4- benzofuranacetamide to label opioid receptor-like 1, μ-, δ- and κ-receptors, respectively. A region-specific up-regulation of the opioid receptor-like 1 receptor (up to 135%) was seen in brains from homozygous mice. μ-Receptors also showed significant differences between genotypes whilst changes in δ- and κ- receptors were minor. In conclusion the region-specific up-regulation of the opioid receptor-like 1 receptor indicates a tonic role for nociceptin/orphanin FQ in some brain structures and may suggest the peptide regulates the receptor expression in these regions. The changes in the opioid receptor-like 1 receptor may relate to the anxiogenic phenotype of these animals but the observed change in μ-receptors does not correlate with altered morphine responses.

Original languageEnglish (US)
Pages (from-to)157-168
Number of pages12
JournalNeuroscience
Volume117
Issue number1
DOIs
StatePublished - Mar 17 2003

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Keywords

  • Denervation supersensitivity
  • Gene deletion
  • Opioid receptor autoradiography
  • Peptide regulation
  • Transgenic

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