Spironolactone as a potential new pharmacotherapy for alcohol use disorder: convergent evidence from rodent and human studies.
Spironolactone as a potential new pharmacotherapy for alcohol use disorder: convergent evidence from rodent and human studies.
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DOI：
10.1038/s41380-022-01736-y
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发表时间：
2022-11
影响因子：
11
通讯作者：
Vendruscolo, Leandro F.
中科院分区：
文献类型：
--
作者：
Farokhnia, Mehdi;Rentsch, Christopher T.;Chuong, Vicky;McGinn, M. Adrienne;Elvig, Sophie K.;Douglass, Eliza A.;Gonzalez, Luis A.;Sanfilippo, Jenna E.;Marchette, Renata C. N.;Tunstall, Brendan J.;Fiellin, David A.;Koob, George F.;Justice, Amy C.;Leggio, Lorenzo;Vendruscolo, Leandro F.
有证据表明，螺内酯，一种非选择性盐皮质激素受体（MR）拮抗剂，调节酒精寻求和消费。因此，安体舒通可能是治疗酒精使用障碍（AUD）的一种新药物。在这项研究中，我们测试了螺内酯在小鼠饮酒模型（黑暗中饮酒）和大鼠酒精依赖模型（蒸汽暴露）中的作用。我们还在美国最大的综合医疗保健系统的药物流行病学队列研究中，使用酒精使用障碍识别测试-消费（AUDIT-C）调查了至少连续60天接受螺内酯与自我报告的酒精消费变化之间的关联。螺内酯剂量依赖性地减少雄性和雌性小鼠对加糖或不加糖酒精溶液的摄入。螺内酯对无酒精的甜味溶液饮用、食物或水摄入、运动协调、酒精诱导的共济失调或血液酒精水平无影响。螺内酯剂量依赖性地减少依赖性和非依赖性雄性和雌性大鼠的操作性酒精自我给药。在人类中，与未接受螺内酯的倾向评分匹配的个体相比，接受螺内酯的个体中观察到饮酒量的更大减少。在基线时报告危险/重度间歇性饮酒（AUDIT-C ≥ 8）的患者和暴露于≥ 50 mg/天螺内酯的患者中，影响最大。这些在啮齿动物和人类研究中的一致发现表明，螺内酯减少了酒精使用，并支持了这种药物可能作为AUD的新型药物疗法进行进一步研究的假设。
Evidence suggests that spironolactone, a nonselective mineralocorticoid receptor (MR) antagonist, modulates alcohol seeking and consumption. Therefore, spironolactone may represent a novel pharmacotherapy for alcohol use disorder (AUD). In this study, we tested the effects of spironolactone in a mouse model of alcohol drinking (drinking-in-the-dark) and in a rat model of alcohol dependence (vapor exposure). We also investigated the association between spironolactone receipt for at least 60 continuous days and change in self-reported alcohol consumption, using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), in a pharmacoepidemiologic cohort study in the largest integrated healthcare system in the US. Spironolactone dose-dependently reduced the intake of sweetened or unsweetened alcohol solutions in male and female mice. No effects of spironolactone were observed on drinking of a sweet solution without alcohol, food or water intake, motor coordination, alcohol-induced ataxia, or blood alcohol levels. Spironolactone dose-dependently reduced operant alcohol self-administration in dependent and nondependent male and female rats. In humans, a greater reduction in alcohol consumption was observed among those who received spironolactone, compared to propensity score-matched individuals who did not receive spironolactone. The largest effects were among those who reported hazardous/heavy episodic alcohol consumption at baseline (AUDIT-C ≥ 8) and those exposed to ≥ 50 mg/day of spironolactone. These convergent findings across rodent and human studies demonstrate that spironolactone reduces alcohol use and support the hypothesis that this medication may be further studied as a novel pharmacotherapy for AUD.
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影响因子：
4.1
作者：
Calvo, N;Volosin, M
通讯作者：
Volosin, M
影响因子：
16.6
作者：
de Guglielmo, Giordano;Kallupi, Marsida;George, Olivier
通讯作者：
George, Olivier
影响因子：
4.6
作者：
Funder, JW
通讯作者：
Funder, JW
影响因子：
20.1
作者：
Good, Miranda E.;Chiu, Yu-Hsin;Ravichandran, Kodi S.
通讯作者：
Ravichandran, Kodi S.
DOI：
10.1073/pnas.0503878102
发表时间：
2006-01-03
影响因子：
11.1
作者：
Berger, S;Wolfer, DP;Schütz, G
通讯作者：
Schütz, G