例如:"lncRNA", "apoptosis", "WRKY"

Genetic Deletion of the Nociceptin/Orphanin FQ Receptor in the Rat Confers Resilience to the Development of Drug Addiction.

Neuropsychopharmacology. 2017 Feb;42(3):695-706. Epub 2016 Aug 26
Marsida Kallupi 1 , Giulia Scuppa 2 , Giordano de Guglielmo 1 , Girolamo Calò 3 , Friedbert Weiss 4 , Michael A Statnick 5 , Linda M Rorick-Kehn 5 , Roberto Ciccocioppo 2
Marsida Kallupi 1 , Giulia Scuppa 2 , Giordano de Guglielmo 1 , Girolamo Calò 3 , Friedbert Weiss 4 , Michael A Statnick 5 , Linda M Rorick-Kehn 5 , Roberto Ciccocioppo 2
+ et al

[No authors listed]

Author information
  • 1 Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
  • 2 School of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, Italy.
  • 3 Department of Medical Science, Section of Pharmacology and National Institute of Neuroscience, University of Ferrara, Ferrara, Italy.
  • 4 Molecular and Cellular Neuroscience Department, The Scripps Research Institute, La Jolla, CA, USA.
  • 5 Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN USA.

摘要


The nociceptin (NOP) receptor is a G-protein-coupled receptor whose natural ligand is the NOP/orphanin FQ (N/OFQ) peptide. Evidence from pharmacological studies suggests that the N/OFQ system is implicated in the regulation of several addiction-related phenomena, such as drug intake, withdrawal, and relapse. Here, to further explore the role of NOP system in addiction, we used NOP (-/-) rats to study the motivation for cocaine, heroin, and alcohol self-administration in the absence of N/OFQ function. Conditioned place preference (CPP) and saccharin (0.2% w/v) self-administration were also investigated. Results showed that NOP (-/-) rats self-administer less cocaine (0.25, 0.125, or 0.5 mg/infusion) both under a fixed ratio 1 and a progressive ratio schedule of reinforcement compared with wild-type (Wt) controls. Consistently, cocaine (10 mg/kg, i.p.) was able to induce CPP in Wt but not in NOP (-/-). When NOP (-/-) rats were tested for heroin (20 μg/infusion) and ethanol (10% v/v) self-administration, they showed significantly lower drug intake compared with Wt. Conversely, saccharin self-administration was not affected by NOP deletion, excluding the possibility of nonspecific learning deficits or generalized disruption of reward mechanisms in NOP (-/-) rats. These findings were confirmed with pharmacological experiments using two selective NOP antagonists, SB-612111 and LY2817412. Both drugs attenuated alcohol self-administration in Wt rats but not in NOP (-/-) rats. In conclusion, our results demonstrate that genetic deletion of NOP receptors confers resilience to drug abuse and support a role for NOP receptor antagonism as a potential treatment option for drug addiction.