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NOP Receptor Antagonists Decrease Alcohol Drinking in the Dark in C57BL/6J Mice
Author(s) -
Brunori Gloria,
Weger Michelle,
Schoch Jennifer,
TargowskaDuda Katarzyna,
Barnes Megan,
Borruto Anna Maria,
RorickKehn Linda M.,
Zaveri Nurulain T.,
Pintar John E.,
Ciccocioppo Roberto,
Toll Lawrence,
Cippitelli Andrea
Publication year - 2019
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.14165
Subject(s) - nop , nociceptin receptor , chemistry , alcohol , receptor , antagonist , pharmacology , receptor antagonist , endocrinology , medicine , binge drinking , ethanol , opioid , opioid peptide , biochemistry , alcohol consumption
Background The nociceptin/orphanin FQ opioid peptide (NOP) receptor and its endogenous ligand N/OFQ have been implicated in the regulation of drug and alcohol use disorders (AUD). In particular, evidence demonstrated that NOP receptor activation blocks reinforcing and motivating effects of alcohol across a range of behavioral measures, including alcohol intake, conditioned place preference, and vulnerability to relapse. Methods Here, we show the effects of pharmacological activation and inhibition of NOP receptors on binge‐like alcohol consumption, as measured by the “drinking in the dark” (DID) model in C57BL/6J mice. Results We found that 2 potent and selective NOP agonists AT‐202 (0, 0.3, 1, 3 mg/kg) and AT‐312 (0, 0.3, 1 mg/kg) did not affect binge alcohol drinking at doses that do not affect locomotor activity. AT‐202 also failed to alter DID behavior when administered to mice previously exposed to chronic alcohol treatment with an alcohol‐containing liquid diet. Conversely, treatment with either the high affinity NOP receptor antagonist SB‐612111 (0, 3, 10, 30 mg/kg) or the selective antagonist LY2817412 (0, 3, 10, 30 mg/kg) decreased binge drinking. SB‐612111 was effective at all doses examined, and LY2817412 was effective at 30 mg/kg. Consistently, NOP receptor knockout mice consumed less alcohol compared to wild type. SB‐612111 reduced DID and increased sucrose consumption at doses that do not appear to affect locomotor activity. However, the high dose of SB‐612111 (30 mg/kg) reduced alcohol intake but failed to inhibit preference in a 2‐bottle choice DID model that can assess moderate alcohol intake. Conclusions The present results suggest that NOP receptor inhibition rather than activation may represent a valuable approach for treatment of AUD characterized by excessive alcohol consumption such as binge drinking.