Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Nov:154:105427.
doi: 10.1016/j.neubiorev.2023.105427. Epub 2023 Oct 17.

Role of aldosterone and mineralocorticoid receptor (MR) in addiction: A scoping review

Claire L Pince  1 , Kimberly E Whiting  2 , Tammy Wang  3 , András H Lékó  4 , Lisa A Farinelli  3 , Diane Cooper  5 , Mehdi Farokhnia  3 , Leandro F Vendruscolo  6 , Lorenzo Leggio  7
Affiliations

Role of aldosterone and mineralocorticoid receptor (MR) in addiction: A scoping review

Claire L Pince et al. Neurosci Biobehav Rev. 2023 Nov.

Abstract

Preclinical and human studies suggest a role of aldosterone and mineralocorticoid receptor (MR) in addiction. This scoping review aimed to summarize (1) the relationship between alcohol and other substance use disorders (ASUDs) and dysfunctions of the aldosterone and MR, and (2) how pharmacological manipulations of MR may affect ASUD-related outcomes. Our search in four databases (MEDLINE, Embase, Web of Science, and Cochrane Library) indicated that most studies focused on the relationship between aldosterone, MR, and alcohol (n = 30), with the rest focused on opioids (n = 5), nicotine (n = 9), and other addictive substances (n = 9). Despite some inconsistencies, the overall results suggest peripheral and central dysregulations of aldosterone and MR in several species and that these dysregulations depended on the pattern of drug exposure and genetic factors. We conclude that MR antagonism may be a promising target in ASUD, yet future studies are warranted.

Keywords: Alcohol; Aldosterone; Mineralocorticoid Receptor; Opioid; Spironolactone; Stimulants.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no competing or conflicts of interest.

Figures

Figure 1.
Figure 1.
The PRISMA flow diagram for the scoping review that details database searches, title and abstract screening, number of full-text articles, and number of articles data was extracted from in the review.
Figure 2.
Figure 2.
The cumulative number of substance use interventional and observational studies involving aldosterone and MR by publication date.
Figure 3.
Figure 3.. Schematic drawing of the effects of chronic alcohol consumption on the renin-angiotensin-aldosterone system and mineralocorticoid receptor (MR).
Chronic alcohol consumption increases both aldosterone and cortisol/corticosterone levels. Aldosterone and cortisol bind MR with equal affinity, while GR only binds cortisol. Intra-striatal and systemic administration of corticosterone but not aldosterone stimulated alcohol intake in adrenalectomized rats. The central amygdala (CeA) is a key brain region implicated in withdrawal and negative affective processes in alcohol use disorder. Expression of the MR-encoding NR3C2 gene in the CeA was also negatively associated with alcohol drinking in rhesus macaques as well as anxiety-like behavior and compulsive-like alcohol drinking in dependent rats, which may represent compensatory downregulation mechanisms related to elevated cortisol levels in alcohol dependence. Knockdown of CeA MRs also transiently reduced alcohol intake in rats. No such associations were found for the PFC or hippocampal MRs. Spironolactone reduces alcohol intake in rodents and humans and intra-CeA eplerenone reduces alcohol intake in rats, suggesting a functional role for MRs in alcohol seeking behaviors.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Agarwal R, Kolkhof P, Bakris G, Bauersachs J, Haller H, Wada T. and Zannad F. (2021). “Steroidal and non-steroidal mineralocorticoid receptor antagonists in cardiorenal medicine.” Eur Heart J 42(2): 152–161. - PMC - PubMed
    1. 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 KA and Leggio L. (2018). “A relationship between the aldosterone-mineralocorticoid receptor pathway and alcohol drinking: preliminary translational findings across rats, monkeys and humans.” Mol Psychiatry 23(6): 1466–1473. - PMC - PubMed
    1. Arksey H. and O’Malley L. (2005). “Scoping studies: towards a methodological framework.” International journal of social research methodology 8(1): 19–32.
    1. Azzam I, Gilad S, Limor R, Stern N. and Greenman Y. (2017). “Ghrelin stimulation by hypothalamic-pituitary-adrenal axis activation depends on increasing cortisol levels.” Endocr Connect 6(8): 847–855. - PMC - PubMed
    1. Balfour DJ, Khullar AK and Longden A. (1975). “Effects of nicotine on plasma corticosterone and brain amines in stressed and unstressed rats.” Pharmacol Biochem Behav 3(2): 179–184. - PubMed

Publication types

MeSH terms

LinkOut - more resources