Ivermectin reduces alcohol intake and preference in mice.
Ivermectin reduces alcohol intake and preference in mice.
复制标题
DOI：
10.1016/j.neuropharm.2012.03.014
复制
发表时间：
2012-08
影响因子：
4.7
通讯作者：
Davies DL
中科院分区：
文献类型：
--
作者：
Yardley MM;Wyatt L;Khoja S;Asatryan L;Ramaker MJ;Finn DA;Alkana RL;Huynh N;Louie SG;Petasis NA;Bortolato M;Davies DL
酒精使用障碍（AUD）治疗失败率很高，这凸显了迫切需要能够阻止乙醇消费的新颖有效的策略。我们小组的最新研究结果表明，伊维菌素 (IVM) 是一种广谱驱虫药，在人类和动物中具有高耐受性和最佳安全性，可拮抗乙醇介导的爪蟾卵母细胞中表达的 P2X4 受体 (P2X4Rs) 抑制。这一发现促使我们推测 IVM 可能会减少饮酒量；因此，在本研究中，我们研究了该药物对雄性和雌性 C57BL/6 小鼠的几种酒精自我给药模型的影响。总体而言，IVM（1.25-10 mg/kg，腹膜内注射）显着减少了 24 小时饮酒量和间歇性限制性饮酒（4 小时）以及操作性酒精自我管理（1 小时）。对酒精摄入量的影响呈剂量依赖性，给药后 9 小时摄入量显着减少，对应于大脑中 IVM 峰值浓度 (Cmax)。 IVM 还显着减少了 24 小时糖精消耗量，但没有改变操作性蔗糖自我施用。综上所述，研究结果表明，IVM 在几种不同的自我给药模型中减少了酒精摄入量，并表明 IVM 可能有助于治疗 AUD。
The high rate of therapeutic failure in the management of alcohol use disorders (AUDs) underscores the urgent need for novel and effective strategies that can deter ethanol consumption. Recent findings from our group showed that ivermectin (IVM), a broad-spectrum anthelmintic with high tolerability and optimal safety profile in humans and animals, antagonized ethanol-mediated inhibition of P2X4 receptors (P2X4Rs) expressed in Xenopus oocytes. This finding prompted us to hypothesize that IVM may reduce alcohol consumption; thus, in the present study we investigated the effects of this agent on several models of alcohol self-administration in male and female C57BL/6 mice. Overall, IVM (1.25–10 mg/kg, intraperitoneal) significantly reduced 24-h alcohol consumption and intermittent limited access (4-h) binge drinking, and operant alcohol self-administration (1-h). The effects on alcohol intake were dose-dependent with the significant reduction in intake at 9 h after administration corresponding to peak IVM concentrations (Cmax) in the brain. IVM also produced a significant reduction in 24-h saccharin consumption, but did not alter operant sucrose self-administration. Taken together, the findings indicate that IVM reduces alcohol intake across several different models of self-administration and suggest that IVM may be useful in the treatment of AUDs.
登录
查看更多内容
影响因子：
3.4
作者：
Finn DA;Mark GP;Fretwell AM;Gililland-Kaufman KR;Strong MN;Ford MM
通讯作者：
Ford MM
DOI：
10.1111/j.1365-2885.2008.01007.x
发表时间：
2009-02-01
影响因子：
1.3
作者：
Geyer, J.;Gavrilova, O.;Petzinger, E.
通讯作者：
Petzinger, E.
影响因子：
11.4
作者：
Buell, G;Lewis, C;Surprenant, A
通讯作者：
Surprenant, A
影响因子：
5.5
作者：
Bouchery, Ellen E.;Harwood, Henrick J.;Brewer, Robert D.
通讯作者：
Brewer, Robert D.
影响因子：
2.7
作者：
Ford, Matthew M.;Mark, Gregory P.;Finn, Deborah A.
通讯作者：
Finn, Deborah A.