RGD Reference Report - Nociceptin/orphanin FQ receptor knockout rats: in vitro and in vivo studies. - Rat Genome Database

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Nociceptin/orphanin FQ receptor knockout rats: in vitro and in vivo studies.

Authors: Rizzi, Anna  Molinari, Stefano  Marti, Matteo  Marzola, Giuliano  Calo', Girolamo 
Citation: Rizzi A, etal., Neuropharmacology. 2011 Mar;60(4):572-9. doi: 10.1016/j.neuropharm.2010.12.010. Epub 2010 Dec 22.
RGD ID: 126925219
Pubmed: PMID:21184763   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neuropharm.2010.12.010   (Journal Full-text)

Nociceptin/orphanin FQ (N/OFQ) regulates several biological functions via selective activation of the N/OFQ peptide (NOP) receptor. Recently knockout rats for the NOP receptor gene (NOP(-/-)) have been generated; these animals were used in the present study to investigate their emotional (open field, elevated plus maze, and forced swimming test), locomotor (drag and rotarod test), and nociceptive (plantar and formalin test) phenotypes in comparison with their NOP(+/+) littermates. In addition, N/OFQ sensitivity has been assessed in electrically stimulated vas deferens tissues taken from NOP(+/+) and NOP(-/-) rats. In the elevated plus maze and forced swimming tests NOP(-/-) rats showed anxiety- and anti-depressant-like phenotype, respectively. No differences were found in the open field test. NOP(-/-) rats outperformed their NOP(+/+) littermates in two motor behaviour assays. Genetic ablation of the NOP receptor gene produced a statistically significant increase in nociceptive behaviour of the mutant rats in the formalin test. Finally, in the electrically stimulated rat vas deferens taken from NOP(+/+) tissues, N/OFQ inhibited in a concentration-dependent manner the electrically induced twitches while the peptide was inactive in tissues taken from NOP(-/-) animals. These results, in line with previous findings obtained with selective NOP receptor antagonists in mice and rats and with mouse knockout studies, clearly indicate that endogenous N/OFQ-NOP receptor signalling plays an important role in controlling anxiety- and mood-related behaviours, exercise-driven locomotor activity and nociception. These observations are relevant for defining the therapeutic indications (and contraindications) of NOP receptor antagonists.

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Objects Annotated

Genes (Rattus norvegicus)
Oprl1  (opioid related nociceptin receptor 1)
Oprl1m1Hubr  (opioid related nociceptin receptor 1; ENU induced mutant1, Hubr)

Strains
WI-Oprl1m1Hubr-/-  (NOPr knockout rat)


Additional Information