NOP Receptor Antagonists Decrease Alcohol Drinking in the Dark in C57BL/6J Mice. (21st August 2019)

• Record Type: Journal Article
• Authors: Brunori, Gloria; Weger, Michelle; Schoch, Jennifer; Targowska‐Duda, Katarzyna; Barnes, Megan; Borruto, Anna Maria; Rorick‐Kehn, Linda M.; Zaveri, Nurulain T.; Pintar, John E.; Ciccocioppo, Roberto; Toll, Lawrence; Cippitelli, Andrea
• Is Part Of: Alcoholism. Volume 43:Number 10(2019)
• Page Start: 2167
• Page End: 2178
• Publication Date: 2019-08-21
• Subjects: Alcohol -- Drinking in the Dark -- SB‐612111 -- NOP Receptor -- N/OFQ; Alcoholism -- Periodicals; Alcoholism -- Periodicals; Alcoolisme; Electronic journals; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.861005
• DOI: 10.1111/acer.14165
• Languages: English
• ISSNs: 0145-6008

Abstract

Abstract : 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. Abstract : Binge drinking represents an enormous public health concern in the United States and worldwide. We report experiments showing that treatment with antagonists of the receptor of the Nociceptin Orphanin FQ Peptide (NOP receptor) decreases excessive alcohol consumption in mouse models of binge‐like alcohol drinking. These experiments demonstrate that NOP receptor inhibition rather than activation represents a valuable approach for treatment of alcohol use disorders characterized by excessive alcohol consumption in humans.