Grigsby Kolter B, Savarese Antonia M, Metten Pamela, Mason Barbara J, Blednov Yuri A, Crabbe John C, Ozburn Angela R
Portland Alcohol Research Center, Department of Behavioral Neuroscience at Oregon Health and Science University and VA Portland Health Care System, Portland, OR, USA.
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.
Neurosci Insights. 2020 Nov 25;15:2633105520975412. doi: 10.1177/2633105520975412. eCollection 2020.
High Drinking in the Dark (HDID-1) mice represent a unique genetic risk model of binge-like drinking and a novel means of screening potential pharmacotherapies to treat alcohol use disorders (AUDs). We tested the effects of tacrolimus (0, 0.5, 1, and 2 mg/kg), sirolimus (0, 5, 10, and 20 mg/kg), palmitoylethanolamide (PEA; 0, 75, 150, and 225 mg/kg), and secukinumab (0, 5, 20, and 60 mg/kg) on binge-like ethanol intake (2-day, "Drinking in the Dark" [DID]) and blood alcohol levels (BALs) in HDID-1 mice. Tacrolimus reduced ethanol intake and BALs. Tacrolimus had no effect on water intake, but reduced saccharin intake. There was no effect of sirolimus, PEA, or secukinumab on ethanol intake or BALs. These results compare and contrast with previous work addressing these compounds or their targeted mechanisms of action on ethanol drinking, highlighting the importance of screening a wide range of models and genotypes to inform the role of neuroimmune signaling in AUDs.
“黑暗中高饮”（HDID-1）小鼠代表了一种独特的类似暴饮的饮酒遗传风险模型，也是筛选治疗酒精使用障碍（AUDs）潜在药物疗法的新方法。我们测试了他克莫司（0、0.5、1和2mg/kg）、西罗莫司（0、5、10和20mg/kg）、棕榈酰乙醇胺（PEA；0、75、150和225mg/kg）以及司库奇尤单抗（0、5、20和60mg/kg）对HDID-1小鼠类似暴饮的乙醇摄入量（2天，“黑暗中饮酒”[DID]）和血液酒精水平（BALs）的影响。他克莫司降低了乙醇摄入量和BALs。他克莫司对水摄入量没有影响，但降低了糖精摄入量。西罗莫司、PEA或司库奇尤单抗对乙醇摄入量或BALs没有影响。这些结果与之前关于这些化合物或其对乙醇饮用的靶向作用机制的研究进行了比较和对比，突出了筛选广泛模型和基因型以了解神经免疫信号在AUDs中的作用的重要性。
