Valentina Sabino1, Jina Kwak, Kenner C Rice, Pietro Cottone. 1. Laboratory of Addictive Disorders, Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, USA. vsabino@bu.edu
Abstract
BACKGROUND: Binge drinking is defined as a pattern of alcohol drinking that brings blood alcohol levels to 80 mg/dl or above. In this study, we pharmacologically characterized the intermittent access to 20% ethanol (EtOH) model (Wise, Psychopharmacologia 1973;29:203) in Sardinian alcohol-preferring (sP) rats to determine to which of the compounds known to reduce drinking in specific animal models this binge-like drinking was sensitive to. METHODS: Adult male sP rats were divided into 2 groups and allowed to drink either 20% v/v alcohol or water for 24 hours on alternate days (Monday, Wednesday, and Friday) or 10% v/v alcohol and water for 24 hours every day. After stabilization of their intake, both groups were administered 3 pharmacological agents with different mechanisms of action, naltrexone-an opioid receptor antagonist, SCH 39166-a dopamine D1 receptor antagonist, and R121919-a Corticotropin-Releasing Factor 1 (CRF1 ) receptor antagonist, and their effects on alcohol and water intake were determined. RESULTS: Intermittent 20% alcohol ("Wise") procedure in sP rats led to binge-like drinking. Alcohol drinking was suppressed by naltrexone and by SCH 39166, but not by R121919. Finally, naltrexone was more potent in reducing alcohol drinking in the intermittent 20% binge-drinking group than in the 10% continuous access drinking group. CONCLUSIONS: The Wise procedure in sP rats induces binge-like drinking, which appears opioid- and dopamine-receptor mediated; the CRF1 system, on the other hand, does not appear to be involved. In addition, our results suggest that naltrexone is particularly effective in reducing binge drinking. Such different pharmacological responses may apply to subtypes of alcoholic patients who differ in their motivation to drink, and may eventually contribute to treatment response.
BACKGROUND: Binge drinking is defined as a pattern of alcohol drinking that brings blood alcohol levels to 80 mg/dl or above. In this study, we pharmacologically characterized the intermittent access to 20% ethanol (EtOH) model (Wise, Psychopharmacologia 1973;29:203) in Sardinian alcohol-preferring (sP) rats to determine to which of the compounds known to reduce drinking in specific animal models this binge-like drinking was sensitive to. METHODS: Adult male sP rats were divided into 2 groups and allowed to drink either 20% v/v alcohol or water for 24 hours on alternate days (Monday, Wednesday, and Friday) or 10% v/v alcohol and water for 24 hours every day. After stabilization of their intake, both groups were administered 3 pharmacological agents with different mechanisms of action, naltrexone-an opioid receptor antagonist, SCH 39166-a dopamine D1 receptor antagonist, and R121919-a Corticotropin-Releasing Factor 1 (CRF1 ) receptor antagonist, and their effects on alcohol and water intake were determined. RESULTS: Intermittent 20% alcohol ("Wise") procedure in sP rats led to binge-like drinking. Alcohol drinking was suppressed by naltrexone and by SCH 39166, but not by R121919. Finally, naltrexone was more potent in reducing alcohol drinking in the intermittent 20% binge-drinking group than in the 10% continuous access drinking group. CONCLUSIONS: The Wise procedure in sP rats induces binge-like drinking, which appears opioid- and dopamine-receptor mediated; the CRF1 system, on the other hand, does not appear to be involved. In addition, our results suggest that naltrexone is particularly effective in reducing binge drinking. Such different pharmacological responses may apply to subtypes of alcoholicpatients who differ in their motivation to drink, and may eventually contribute to treatment response.
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