Irene Lorrai1,2,3, Chase Shankula4, Jorge Marquez Gaytan4, Tomoya Kawamura4, Paola Maccioni5, Claudia Mugnaini6, Federico Corelli6, Gian Luigi Gessa7,5, Pietro Paolo Sanna4, Giancarlo Colombo5. 1. Department of Immunology and Microbiology, The Scripps Research Institute, 10550 North Torrey Pines Road, MB-114, La Jolla, CA, 92037, USA. ilorrai@scripps.edu. 2. Department of Biomedical Sciences, University of Cagliari, (CA), I-09042, Monserrato, Italy. ilorrai@scripps.edu. 3. Neuroscience Institute, Section of Cagliari, National Research Council of Italy, I-09042, Monserrato, CA, Italy. ilorrai@scripps.edu. 4. Department of Immunology and Microbiology, The Scripps Research Institute, 10550 North Torrey Pines Road, MB-114, La Jolla, CA, 92037, USA. 5. Neuroscience Institute, Section of Cagliari, National Research Council of Italy, I-09042, Monserrato, CA, Italy. 6. Department of Biotechnology, Chemistry, and Pharmacy, University of Siena, I-53100, Siena, SI, Italy. 7. Department of Biomedical Sciences, University of Cagliari, (CA), I-09042, Monserrato, Italy.
Abstract
RATIONALE: Binge drinking (BD) is a widespread drinkingpattern that may contribute to promote the development of alcohol use disorder (AUD). The comprehension of its neurobiological basis and the identification of molecules that may prevent BD are critical. Preclinical studies demonstrated that positive allosteric modulators (PAMs) of the GABAB receptor effectively reduced, and occasionally suppressed, the reinforcing and motivational properties of alcohol in rodents, suggesting their potential use as pharmacotherapy for AUD, including BD. Recently, we demonstrated that COR659, a novel GABAB PAM, effectively reduced (i) alcohol drinking under the 2-bottle choice regimen, (ii) alcohol self-administration under both fixed and progressive ratio schedules of reinforcement, and (iii) cue-induced reinstatement of alcohol-seeking behavior in Sardinian alcohol-preferring (sP) rats. OBJECTIVES: The present study investigated whether the "anti-alcohol" properties of COR659 extend to binge-like drinking in rodents. METHODS: COR659 was tested on the "drinking in the dark" (DID) paradigm in C57BL/6J mice and the 4-bottle "alcohol [10%, 20%, 30% (v/v)] versus water" choice regimen with limited and unpredictable access to alcohol in sP rats. RESULTS: Acute administration of non-sedative doses of COR659 (10, 20, and 40 mg/kg; i.p.) effectively and selectively suppressed the intake of intoxicating amounts of alcohol (> 2 g/kg) consumed by C57BL/6J mice and sP rats exposed to these binge-like drinking experimental procedures. CONCLUSIONS: The present data demonstrate the ability of COR659 to suppress binge-like drinking in rodents and strengthen the hypothesis that GABAB PAMs may represent a potentially effective pharmacotherapy for alcohol misuse.
RATIONALE: Binge drinking (BD) is a widespread drinkingpattern that may contribute to promote the development of alcohol use disorder (AUD). The comprehension of its neurobiological basis and the identification of molecules that may prevent BD are critical. Preclinical studies demonstrated that positive allosteric modulators (PAMs) of the GABAB receptor effectively reduced, and occasionally suppressed, the reinforcing and motivational properties of alcohol in rodents, suggesting their potential use as pharmacotherapy for AUD, including BD. Recently, we demonstrated that COR659, a novel GABAB PAM, effectively reduced (i) alcohol drinking under the 2-bottle choice regimen, (ii) alcohol self-administration under both fixed and progressive ratio schedules of reinforcement, and (iii) cue-induced reinstatement of alcohol-seeking behavior in Sardinian alcohol-preferring (sP) rats. OBJECTIVES: The present study investigated whether the "anti-alcohol" properties of COR659 extend to binge-like drinking in rodents. METHODS: COR659 was tested on the "drinking in the dark" (DID) paradigm in C57BL/6J mice and the 4-bottle "alcohol [10%, 20%, 30% (v/v)] versus water" choice regimen with limited and unpredictable access to alcohol in sP rats. RESULTS: Acute administration of non-sedative doses of COR659 (10, 20, and 40 mg/kg; i.p.) effectively and selectively suppressed the intake of intoxicating amounts of alcohol (> 2 g/kg) consumed by C57BL/6J mice and sP rats exposed to these binge-like drinking experimental procedures. CONCLUSIONS: The present data demonstrate the ability of COR659 to suppress binge-like drinking in rodents and strengthen the hypothesis that GABAB PAMs may represent a potentially effective pharmacotherapy for alcohol misuse.
Authors: Roberta Agabio; Julia Ma Sinclair; Giovanni Addolorato; Henri-Jean Aubin; Esther M Beraha; Fabio Caputo; Jonathan D Chick; Patrick de La Selle; Nicolas Franchitto; James C Garbutt; Paul S Haber; Mathis Heydtmann; Philippe Jaury; Anne R Lingford-Hughes; Kirsten C Morley; Christian A Müller; Lynn Owens; Adam Pastor; Louise M Paterson; Fanny Pélissier; Benjamin Rolland; Amanda Stafford; Andrew Thompson; Wim van den Brink; Renaud de Beaurepaire; Lorenzo Leggio Journal: Lancet Psychiatry Date: 2018-11-06 Impact factor: 27.083
Authors: Andrea Balla; Bin Dong; Borehalli M Shilpa; Kiran Vemuri; Alexandros Makriyannis; Subhash C Pandey; Henry Sershen; Raymond F Suckow; K Yaragudri Vinod Journal: Neuropharmacology Date: 2017-11-03 Impact factor: 5.250
Authors: Eric Augier; Russell S Dulman; Ruslan Damadzic; Andrew Pilling; J Paul Hamilton; Markus Heilig Journal: Neuropsychopharmacology Date: 2017-03-15 Impact factor: 7.853