National Institute on Drug Abuse Intramural Research Program

Featured Paper of the Month – November 2017

This paper describes three separate studies, conducted with non-human primates, rats, and humans, that investigated the potential contribution of the hormone aldosterone and its mineralocorticoid receptor to alcohol use disorder. Taken together, these findings suggest a relationship between excessive alcohol use, alcohol use disorder, and specific changes in the aldosterone/ mineralocorticoid receptor pathway marked by increased circulating aldosterone and decreased mineralocorticoid receptor gene expression in the amygdala. Future studies should further investigate the mechanisms underlying the relationship between alcohol drinking and the aldosterone/ mineralocorticoid receptor pathway and whether this pathway might be targeted for the development of new pharmacotherapies for alcohol use disorder.

Publication Information

Aoun, E G; Jimenez, V A; Vendruscolo, L F; Walter, N A R; Barbier, E; Ferrulli, A; Haass-Koffler, C L; Darakjian, P; Lee, M R; Addolorato, G; Heilig, M; Hitzemann, R; Koob, G F; Grant, K A; Leggio, L

A relationship between the aldosterone-mineralocorticoid receptor pathway and alcohol drinking: preliminary translational findings across rats, monkeys and humans. Journal Article

In: Mol Psychiatry, 2017, ISSN: 1476-5578 (Electronic); 1359-4184 (Linking).

Abstract | Links

@article{Aoun:2017aa,

title = {A relationship between the aldosterone-mineralocorticoid receptor pathway and alcohol drinking: preliminary translational findings across rats, monkeys and humans.},

author = {E G Aoun and V A Jimenez and L F Vendruscolo and N A R Walter and E Barbier and A Ferrulli and C L Haass-Koffler and P Darakjian and M R Lee and G Addolorato and M Heilig and R Hitzemann and G F Koob and K A Grant and L Leggio},

url = {https://www.ncbi.nlm.nih.gov/pubmed/28461696},

doi = {10.1038/mp.2017.97},

issn = {1476-5578 (Electronic); 1359-4184 (Linking)},

year  = {2017},

date = {2017-05-02},

urldate = {2017-05-02},

journal = {Mol Psychiatry},

address = {Department of Psychiatry and Human Behavior, Brown University Medical School, Providence, RI, USA.},

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.Molecular Psychiatry advance online publication, 2 May 2017; doi:10.1038/mp.2017.97.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

A relationship between the aldosterone-mineralocorticoid receptor pathway and alcohol drinking: preliminary translational findings across rats, monkeys and humans.