Yardley Megan M, Neely Michael, Huynh Nhat, Asatryan Liana, Louie Stan G, Alkana Ronald L, Davies Daryl L
aDepartment of Pharmacology and Pharmaceutical Sciences bTitus Family Department of Clinical Pharmacy and Pharmaceutical Economics and Policy, School of Pharmacy cDepartment of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Neuroreport. 2014 Sep 10;25(13):1018-23. doi: 10.1097/WNR.0000000000000211.
Ivermectin (IVM), an FDA approved anthelmintic agent, can significantly reduce ethanol intake in mice following acute administration. The current study evaluates the sustainability and safety of multiday IVM administration in reducing 10% v/v ethyl alcohol (10E) intake in mice at a dose shown to be safe in humans. We tested the effect of 10-day administration of IVM (3.0 mg/kg/day; intraperitoneally) on reducing 10E intake in C57BL/6J mice using a 24-h, two-bottle choice paradigm. On the 10th day of IVM administration, mice were sacrificed at 0, 0.5, 2, 8, 32, 48, and 72 h after injection. Brain tissue and plasma samples were collected and analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Analysis of variance (ANOVA) was used to assess the effect of 10-day IVM administration on 10E intake, 10E preference, water intake, and total fluid intake with Dunnett's multiple comparison post-hoc test. Individual Student's t-tests were also used to further quantify changes in these dependent variables. IVM significantly decreased 10E intake over a 9-day period (P<0.01). Pre-IVM 10E intake was 9.1±3.2 g/kg/24 h. Following the 9th day of IVM injections, intake dropped by almost 30% (P<0.05). IVM had no effect on total water intake or mouse weight throughout the study; however, there was a significant decrease in both preference for 10E (P<0.01) and total fluid intake (P<0.05). Multiday administration of IVM significantly reduces 10E intake and preference in animals without causing any apparent adverse effects at a dose shown to be safe in humans.
伊维菌素（IVM）是一种经美国食品药品监督管理局（FDA）批准的驱虫剂，急性给药后可显著减少小鼠的乙醇摄入量。本研究评估了多日给予IVM在减少小鼠10%（体积/体积）乙醇（10E）摄入量方面的可持续性和安全性，该剂量在人体中显示是安全的。我们使用24小时双瓶选择范式，测试了连续10天腹腔注射IVM（3.0毫克/千克/天）对减少C57BL/6J小鼠10E摄入量的影响。在IVM给药的第10天，在注射后0、0.5、2、8、32、48和72小时处死小鼠。收集脑组织和血浆样本，并使用液相色谱-串联质谱法（LC-MS/MS）进行分析。采用方差分析（ANOVA）评估连续10天给予IVM对10E摄入量、10E偏好、水摄入量和总液体摄入量的影响，并进行Dunnett多重比较事后检验。还使用个体学生t检验进一步量化这些因变量的变化。IVM在9天内显著降低了10E摄入量（P<0.01）。IVM注射前10E摄入量为9.1±3.2克/千克/24小时。在IVM注射第9天后，摄入量下降了近30%（P<0.05）。在整个研究过程中，IVM对总水摄入量或小鼠体重没有影响；然而，对10E的偏好（P<0.01）和总液体摄入量（P<0.05）均显著降低。多日给予IVM可显著降低动物的10E摄入量和偏好，且在人体显示安全的剂量下不会引起任何明显的不良反应。
