Complete knockout of the nociceptin/orphanin FQ receptor in the rat does not induce compensatory changes in mu, delta and kappa opioid receptors.

J.R. Homberg, J.D. Mul, E. de Wit, E. Cuppen

Research output: Contribution to journal/periodicalArticleScientificpeer-review

37 Citations (Scopus)

Abstract

The nociceptin/orphanin FQ (N/OFQ) opioid peptide receptor (NOPr) is a new member of the opioid receptor family consisting of mu, delta and kappa opioid receptors. The anti-opioid properties of its endogenous ligand, N/OFQ provide the receptor interesting potentials in symptoms and processes related to drug addiction, learning and memory, anxiety and depression, and nociception. Using target-selected N-ethyl-N-nitrosourea (ENU)-driven mutagenesis we recently generated a rat model bearing a premature stop codon in the opioid-like receptor (oprl1) gene, and here we describe the primary characterization of this novel model. Data revealed that [(3)H]N/OFQ binding to brain slices was completely absent in rats homozygous for the premature stop codon (oprl1(-/-)). Heterozygous rats displayed an intermediate level of NOPr binding. Oprl1 receptor transcript levels, as determined by Northern blot analysis, were reduced by approximately 50% in oprl1(-/-) rats compared to wild-type controls (oprl1(+/+)), and no alternative spliced transcripts were observed. Quantitative autoradiographic mapping of mu, delta and kappa opioid receptors using [(3)H]DAMGO, [(3)H]deltorphin and [(3)H]CI-977, respectively, did not show any changes in opioid receptor binding. In conclusion, we present a novel mutant rat lacking NOPr without compensatory changes in mu, delta and kappa opioid receptors. We anticipate that this mutant rat will have heuristic value to further understand the function of NOPr.
Original languageEnglish
Pages (from-to)308-315
JournalNeuroscience
Volume163
Issue number1
DOIs
Publication statusPublished - 2009

Fingerprint

Dive into the research topics of 'Complete knockout of the nociceptin/orphanin FQ receptor in the rat does not induce compensatory changes in mu, delta and kappa opioid receptors.'. Together they form a unique fingerprint.

Cite this