RGD Reference Report - Pharmacological blockade or genetic knockout of the NOP receptor potentiates the rewarding effect of morphine in rats. - Rat Genome Database

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Pharmacological blockade or genetic knockout of the NOP receptor potentiates the rewarding effect of morphine in rats.

Authors: Rutten, Kris  De Vry, Jean  Bruckmann, Walter  Tzschentke, Thomas M 
Citation: Rutten K, etal., Drug Alcohol Depend. 2011 Apr 1;114(2-3):253-6. doi: 10.1016/j.drugalcdep.2010.10.004. Epub 2010 Nov 20.
RGD ID: 14348962
Pubmed: PMID:21095077   (View Abstract at PubMed)
DOI: DOI:10.1016/j.drugalcdep.2010.10.004   (Journal Full-text)

The Nociceptin/OrphaninFQ (NOP) system is believed to be involved in drug abuse and addiction. We have recently demonstrated that activation of the NOP receptor, by systemic administration of the NOP receptor agonist Ro65-6570, attenuated the rewarding effect of various opioids in conditioned place preference (CPP) in rats and this attenuating effect was reversed by the NOP receptor antagonist J-113397. The present study demonstrates that co-administration of J-113397 (4.64 mg/kg, i.p.) during conditioning, facilitates morphine-induced CPP. Moreover, we found that NOP receptor knockout rats (oprl1(-/-)) are more sensitive to the rewarding effect of morphine than wildtype control rats. Thus, pharmacological or genetic inactivation of the NOP system rendered rats more susceptible to the rewarding effect of morphine. These findings support the suggestion that the endogenous NOP system attenuates the rewarding effect of opioids and therefore offers a therapeutic target for the treatment of drug abuse and addiction.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Oprl1Ratconditioned place preference  IMP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Oprl1Ratenhanced conditioned place preference behavior  IMP  RGD 
Oprl1m1HubrRatenhanced conditioned place preference behavior  IMP  RGD 
WI-Oprl1m1Hubr-/-Ratenhanced conditioned place preference behavior  IMP morphine: morphine hydrochloride trihydrate CHEBI:55348RGD 
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