Department of Psychiatry and Human Behavior, Brown University Medical School, Providence, RI, USA.
Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA.
Mol Psychiatry. 2018 Jun;23(6):1466-1473. doi: 10.1038/mp.2017.97. Epub 2017 May 2.
Aldosterone regulates electrolyte and fluid homeostasis through binding to the mineralocorticoid receptors (MRs). Previous work provides evidence for a role of aldosterone in alcohol use disorders (AUDs). We tested the hypothesis that high functional activity of the mineralocorticoid endocrine pathway contributes to vulnerability for AUDs. In Study 1, we investigated the relationship between plasma aldosterone levels, ethanol self-administration and the expression of CYP11B2 and MR (NR3C2) genes in the prefrontal cortex area (PFC) and central nucleus of the amygdala (CeA) in monkeys. Aldosterone significantly increased after 6- and 12-month ethanol self-administration. NR3C2 expression in the CeA was negatively correlated to average ethanol intake during the 12 months. In Study 2, we measured Nr3c2 mRNA levels in the PFC and CeA of dependent and nondependent rats and the correlates with ethanol drinking during acute withdrawal. Low Nr3c2 expression levels in the CeA were significantly associated with increased anxiety-like behavior and compulsive-like drinking in dependent rats. In Study 3, the relationship between plasma aldosterone levels, alcohol drinking and craving was investigated in alcohol-dependent patients. Non-abstinent patients had significantly higher aldosterone levels than abstinent patients. Aldosterone levels positively correlated with the number of drinks consumed, craving and anxiety scores. These findings support a relationship between ethanol drinking and the aldosterone/MR pathway in three different species.
醛固酮通过与盐皮质激素受体 (MRs) 结合来调节电解质和液体稳态。先前的工作为醛固酮在酒精使用障碍 (AUDs) 中的作用提供了证据。我们测试了这样一个假设,即醛固酮内分泌途径的高功能活性有助于 AUDs 的易感性。在研究 1 中,我们研究了血浆醛固酮水平、乙醇自我给药以及 CYP11B2 和 MR(NR3C2)基因在猴子前额叶皮层 (PFC) 和杏仁中央核 (CeA) 中的表达之间的关系。醛固酮在 6 个月和 12 个月乙醇自我给药后显著增加。CeA 中的 NR3C2 表达与 12 个月期间的平均乙醇摄入量呈负相关。在研究 2 中,我们测量了依赖和非依赖大鼠 PFC 和 CeA 中的 Nr3c2 mRNA 水平,并与急性戒断期间的乙醇饮用相关。CeA 中低 Nr3c2 表达水平与依赖大鼠的焦虑样行为和强迫性饮酒增加显著相关。在研究 3 中,我们研究了酒精依赖患者的血浆醛固酮水平、饮酒和渴望之间的关系。未戒酒的患者的醛固酮水平明显高于戒酒的患者。醛固酮水平与饮酒量、渴望和焦虑评分呈正相关。这些发现支持了三种不同物种中乙醇饮用与醛固酮/MR 途径之间的关系。