A relationship between the aldosterone-mineralocorticoid receptor pathway and alcohol drinking

Preliminary translational findings across rats, monkeys and humans

E. G. Aoun, V. A. Jimenez, L. F. Vendruscolo, N. A.R. Walter, E. Barbier, A. Ferrulli, C. L. Haass-Koffler, P. Darakjian, M. R. Lee, G. Addolorato, M. Heilig, Robert Hitzemann, G. F. Koob, Kathleen (Kathy) Grant, L. Leggio

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1466-1473
Number of pages8
JournalMolecular Psychiatry
Volume23
Issue number6
DOIs
StatePublished - Jun 1 2018

Fingerprint

Mineralocorticoid Receptors
Aldosterone
Alcohol Drinking
Haplorhini
Ethanol
Drinking
Self Administration
Alcohols
Prefrontal Cortex
Anxiety
Cytochrome P-450 CYP11B2
Compulsive Behavior
Mineralocorticoids
Electrolytes
Homeostasis
Messenger RNA
Central Amygdaloid Nucleus
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

A relationship between the aldosterone-mineralocorticoid receptor pathway and alcohol drinking : Preliminary translational findings across rats, monkeys and humans. / 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, Robert; Koob, G. F.; Grant, Kathleen (Kathy); Leggio, L.

In: Molecular Psychiatry, Vol. 23, No. 6, 01.06.2018, p. 1466-1473.

Research output: Contribution to journalArticle

Aoun, EG, Jimenez, VA, Vendruscolo, LF, Walter, NAR, Barbier, E, Ferrulli, A, Haass-Koffler, CL, Darakjian, P, Lee, MR, Addolorato, G, Heilig, M, Hitzemann, R, Koob, GF, Grant, KK & Leggio, L 2018, 'A relationship between the aldosterone-mineralocorticoid receptor pathway and alcohol drinking: Preliminary translational findings across rats, monkeys and humans', Molecular Psychiatry, vol. 23, no. 6, pp. 1466-1473. https://doi.org/10.1038/mp.2017.97
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, Robert ; Koob, G. F. ; Grant, Kathleen (Kathy) ; Leggio, L. / A relationship between the aldosterone-mineralocorticoid receptor pathway and alcohol drinking : Preliminary translational findings across rats, monkeys and humans. In: Molecular Psychiatry. 2018 ; Vol. 23, No. 6. pp. 1466-1473.
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