High Drinking in the Dark (HDID) mice are sensitive to the effects of some clinically relevant drugs to reduce binge-like drinking.
High Drinking in the Dark (HDID) mice are sensitive to the effects of some clinically relevant drugs to reduce binge-like drinking.
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DOI：
10.1016/j.pbb.2017.08.002
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发表时间：
2017-09
期刊：
影响因子：
--
通讯作者：
Huang LC
中科院分区：
文献类型：
--
作者：
Crabbe JC;Ozburn AR;Metten P;Barkley-Levenson A;Schlumbohm JP;Spence SE;Hack WR;Huang LC
有一个严重的公共卫生需要更好地了解酒精使用障碍的疾病机制和改善治疗。在撰写本文时，只有三种药物被食品和药物管理局批准作为治疗酒精使用障碍的药物-双硫仑，纳洛酮和阿坎酸。酗酒是一种滥用酒精的饮酒形式，由NIAAA定义为在大约2小时的时间内饮酒至血液酒精水平（巴尔斯）> 0.08%。为了模拟酗酒的遗传风险，我们使用选择性育种来创建一种独特的动物模型，黑暗中的高饮酒（HDID）小鼠。HDID小鼠的行为表征揭示了HDID小鼠在饮酒后表现出行为障碍，在单次狂饮后戒断，并且响应于诱导连续的依赖性循环而增加其摄入。值得注意的是，HDID小鼠没有表现出味觉偏好或酒精清除率的改变。因此，我们询问已知临床相关性的药物是否可以调节HDID小鼠中的酗酒样乙醇饮用，推理HDID反应的这种表征应该为将来使用这种遗传动物模型筛选和开发新的潜在治疗方法提供信息。我们测试了阿坎酸和纳洛酮减少HDID小鼠中的暴饮暴食的功效。此外，我们测试了GABAB受体激动剂巴氯芬，根据最近的临床前和临床研究表明，它可以减少饮酒。由于双硫仑的临床使用更为有限，我们选择不纳入双硫仑。在限制进入的黑暗中饮酒（DID）范例中，在急性剂量的药物后对小鼠进行测试。HDID小鼠对阿坎酸和巴氯芬的作用敏感，但对纳洛酮不敏感。这两种药物都能减少暴饮暴食。然而，纳洛酮未能减少HDID小鼠的饮酒。因此，HDID小鼠可以代表用于筛选新化合物的有用模型。
There is a serious public health need for better understanding of alcohol use disorder disease mechanisms and for improved treatments. At this writing, only three drugs are approved by the Food and Drug Administration as medications to treat alcohol use disorders – disulfiram, naltrexone, and acamprosate. Binge drinking is a form of abusive alcohol drinking defined by the NIAAA as a drinking to blood alcohol levels (BALs) > 0.08% during a period of approximately 2 hr. To model genetic risk for binge-like drinking, we have used selective breeding to create a unique animal model, High Drinking in the Dark (HDID) mice. Behavioral characterization of HDID mice has revealed that HDID mice exhibit behavioral impairment after drinking, withdrawal after a single binge-drinking session, and escalate their intake in response to induction of successive cycles of dependence. Notably, HDID mice do not exhibit altered tastant preference or alcohol clearance rates. We therefore asked whether drugs of known clinical relevance could modulate binge-like ethanol drinking in HDID mice, reasoning that this characterization of HDID responses should inform future use of this genetic animal model for screening and development of novel potential therapeutics. We tested the efficacy of acamprosate and naltrexone to reduce binge-like drinking in HDID mice. Additionally, we tested the GABAB receptor agonist, baclofen, based on recent pre-clinical and clinical studies demonstrating that it reduces alcohol drinking. We elected not to include disulfiram due to its more limited clinical usage. Mice were tested after acute doses of drugs in the limited-access Drinking in the Dark (DID) paradigm. HDID mice were sensitive to the effects of acamprosate and baclofen, but not naltrexone. Both drugs reduced binge-like drinking. However, naltrexone failed to reduce drinking in HDID mice. Thus, HDID mice may represent a useful model for screening novel compounds.
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影响因子：
3.6
作者：
Bell, Richard L.;Sable, Helen J. K.;Colombo, Giancarlo;Hyytia, Petri;Rodd, Zachary A.;Lumeng, Lawrence
通讯作者：
Lumeng, Lawrence
影响因子：
34.7
作者：
Heilig, Markus;Goldman, David;Berrettini, Wade;O'Brien, Charles P.
通讯作者：
O'Brien, Charles P.
影响因子：
2.8
作者：
Brager AJ;Prosser RA;Glass JD
通讯作者：
Glass JD
影响因子：
3.4
作者：
Barkley-Levenson AM;Cunningham CL;Smitasin PJ;Crabbe JC
通讯作者：
Crabbe JC
DOI：
10.1111/gbb.12105
发表时间：
2014-02
期刊：
Genes, brain, and behavior
影响因子：
--
作者：
Crabbe JC;Metten P;Belknap JK;Spence SE;Cameron AJ;Schlumbohm JP;Huang LC;Barkley-Levenson AM;Ford MM;Phillips TJ
通讯作者：
Phillips TJ