Laboratory of Addictive Disorders, Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, USA.
Alcohol Clin Exp Res. 2013 Apr;37(4):635-43. doi: 10.1111/acer.12008. Epub 2012 Nov 5.
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.
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.
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.
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.
狂饮被定义为一种饮酒模式,会导致血液酒精水平达到 80mg/dl 或以上。在这项研究中,我们对撒丁岛酒精偏好(sP)大鼠的间歇性接触 20%乙醇(EtOH)模型(Wise,Psychopharmacologia 1973;29:203)进行了药理学表征,以确定哪些化合物对这种类似狂欢的饮酒敏感,这些化合物已知可减少特定动物模型中的饮酒量。
成年雄性 sP 大鼠分为两组,一组连续 24 小时饮用 20%v/v 酒精或水,另一组连续 24 小时饮用 10%v/v 酒精和水。在稳定其摄入量后,两组均给予 3 种具有不同作用机制的药理学药物,纳曲酮-阿片受体拮抗剂、SCH 39166-多巴胺 D1 受体拮抗剂和 R121919-促肾上腺皮质素释放因子 1(CRF1)受体拮抗剂,并测定它们对酒精和水摄入量的影响。
sP 大鼠的间歇性 20%酒精(“Wise”)程序导致狂欢式饮酒。酒精摄入量被纳曲酮和 SCH 39166 抑制,但不受 R121919 抑制。最后,纳曲酮在减少间歇性 20%狂欢性饮酒组的酒精饮用量方面比在 10%连续摄入组更为有效。
sP 大鼠的 Wise 程序诱导类似狂欢的饮酒,这似乎是阿片类和多巴胺受体介导的;另一方面,CRF1 系统似乎不参与。此外,我们的结果表明,纳曲酮特别有效地减少狂欢性饮酒。这些不同的药理反应可能适用于不同饮酒动机的酒精患者亚类,最终可能有助于治疗反应。