@article{95fa906451d54a5591bf5d20361ffd60,
title = "A relationship between the aldosterone-mineralocorticoid receptor pathway and alcohol drinking: Preliminary translational findings across rats, monkeys and humans",
abstract = "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.",
author = "Aoun, {E. G.} and Jimenez, {V. A.} and Vendruscolo, {L. F.} and Walter, {N. A.R.} and E. Barbier and A. Ferrulli and Haass-Koffler, {C. L.} and P. Darakjian and Lee, {M. R.} and G. Addolorato and M. Heilig and R. Hitzemann and Koob, {G. F.} and Grant, {K. A.} and L. Leggio",
note = "Funding Information: We thank the following funding sources: European Foundation for Alcohol Research (ERAB) Grant EA0619 (to LL, GA) and ERAB exchange award EXA0802 (to LL); National Institutes of Health (NIH) intramural funding ZIA-AA000218 (Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology; to LL), jointly supported by the Division of Intramural Clinical and Biological Research of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the Intramural Research Program of the National Institute on Drug Abuse (NIDA); National Institute of Mental Health Grant MH101076 (research protected time for EGA under R25 mechanism); the Swedish Research Council (BE, MH); the Pearson Center for Alcoholism and Addiction Research (to LFV, GFK); and NIAAA Grants AA023867 (to CLH-K), AA010760 (to RH), AA08459 (to LFV, GFK) and AA109431 (to KAG). We also thank Karen Smith (NIH Library) for bibliographic assistance, Lisa Farinelli (Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse) for providing support with the preparation of the manuscript and Dr Christa Helms for initial data organization. Publisher Copyright: {\textcopyright} 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.",
year = "2018",
month = jun,
day = "1",
doi = "10.1038/mp.2017.97",
language = "English (US)",
volume = "23",
pages = "1466--1473",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",
number = "6",
}