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NOP Receptor Antagonists Decrease Alcohol Drinking in the Dark in C57BL/6J Mice.

Gloria Brunori1,2,3, Michelle Weger2, Jennifer Schoch1,2

  • 1Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida.

Alcoholism, Clinical and Experimental Research
|August 7, 2019
PubMed
Summary
This summary is machine-generated.

NOP receptor inhibition, not activation, may treat alcohol use disorders. Blocking NOP receptors reduced binge drinking in mice, suggesting a new therapeutic strategy for excessive alcohol consumption.

Keywords:
AlcoholDrinking in the DarkN/OFQNOP ReceptorSB-612111

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Addiction Research

Background:

  • The nociceptin/orphanin FQ (NOP) opioid peptide receptor and its ligand are involved in regulating alcohol use disorders (AUD).
  • NOP receptor activation has been shown to reduce alcohol's reinforcing and motivating effects.
  • Previous research indicates a role for NOP receptors in alcohol intake, preference, and relapse vulnerability.

Purpose of the Study:

  • To investigate the effects of pharmacological NOP receptor activation and inhibition on binge-like alcohol consumption.
  • To evaluate NOP receptor antagonists and agonists in mouse models of alcohol intake.

Main Methods:

  • Utilized the "drinking in the dark" (DID) model in C57BL/6J mice to measure binge alcohol consumption.
  • Administered selective NOP receptor agonists (AT-202, AT-312) and antagonists (SB-612111, LY2817412).
  • Assessed effects on locomotor activity and compared alcohol consumption in NOP receptor knockout mice versus wild-type mice.

Main Results:

  • NOP receptor agonists did not affect binge alcohol drinking or locomotor activity.
  • NOP receptor antagonists (SB-612111, LY2817412) significantly decreased binge alcohol consumption.
  • NOP receptor knockout mice exhibited reduced alcohol consumption compared to wild-type controls.
  • SB-612111 reduced DID behavior and increased sucrose consumption without affecting locomotor activity.

Conclusions:

  • NOP receptor inhibition, rather than activation, shows potential for treating alcohol use disorders characterized by excessive consumption.
  • Targeting NOP receptors may offer a novel therapeutic strategy for conditions like binge drinking.