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NOP Receptor Antagonists Decrease Alcohol Drinking in the Dark in C57BL/6J Mice.
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.
Afiliação
  • Brunori G; Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida.
  • Weger M; Torrey Pines Institute for Molecular Studies, Port St. Lucie, Florida.
  • Schoch J; Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy.
  • Targowska-Duda K; Torrey Pines Institute for Molecular Studies, Port St. Lucie, Florida.
  • Barnes M; Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida.
  • Borruto AM; Torrey Pines Institute for Molecular Studies, Port St. Lucie, Florida.
  • Rorick-Kehn LM; Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida.
  • Zaveri NT; Department of Biopharmacy, Medical University of Lublin, Lublin, Poland.
  • Pintar JE; Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida.
  • Ciccocioppo R; Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy.
  • Toll L; Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana.
  • Cippitelli A; Astraea Therapeutics Inc., Mountain View, California.
Alcohol Clin Exp Res ; 43(10): 2167-2178, 2019 10.
Article em En | MEDLINE | ID: mdl-31386211
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Consumo de Bebidas Alcoólicas / Receptores Opioides / Dissuasores de Álcool / Antagonistas de Entorpecentes Limite: Animals Idioma: En Revista: Alcohol Clin Exp Res Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Consumo de Bebidas Alcoólicas / Receptores Opioides / Dissuasores de Álcool / Antagonistas de Entorpecentes Limite: Animals Idioma: En Revista: Alcohol Clin Exp Res Ano de publicação: 2019 Tipo de documento: Article