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A relationship between the aldosterone-mineralocorticoid receptor pathway and alcohol drinking: preliminary translational findings across rats, monkeys and humans
Brown Univ, RI 02912 USA.
Oregon Hlth and Sci Univ, OR 97201 USA.
Scripps Res Inst, CA 92037 USA; NIDA, MD 20892 USA.
Oregon Hlth and Sci Univ, OR 97201 USA.
Vise andre og tillknytning
2018 (engelsk)Inngår i: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 23, nr 6, s. 1466-1473Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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.

sted, utgiver, år, opplag, sider
NATURE PUBLISHING GROUP , 2018. Vol. 23, nr 6, s. 1466-1473
HSV kategori
Identifikatorer
URN: urn:nbn:se:liu:diva-149720DOI: 10.1038/mp.2017.97ISI: 000437225900008PubMedID: 28461696OAI: oai:DiVA.org:liu-149720DiVA, id: diva2:1234389
Merknad

Funding Agencies|European Foundation for Alcohol Research (ERAB) [EA0619]; ERAB exchange award [EXA0802]; National Institutes of Health (NIH) [ZIA-AA000218]; Division of Intramural Clinical and Biological Research of the National Institute on Alcohol Abuse and Alcoholism (NIAAA); Intramural Research Program of the National Institute on Drug Abuse (NIDA); National Institute of Mental Health [MH101076]; Swedish Research Council; Pearson Center for Alcoholism and Addiction Research; NIAAA [AA023867, AA010760, AA08459, AA109431]

Tilgjengelig fra: 2018-07-24 Laget: 2018-07-24 Sist oppdatert: 2018-08-14

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