A relationship between the aldosterone-mineralocorticoid receptor pathway and alcohol drinking: preliminary translational findings across rats, monkeys and humans
| Autor: | Priscila Darakjian, Leandro F. Vendruscolo, Carolina L. Haass-Koffler, Lorenzo Leggio, Giovanni Addolorato, Markus Heilig, Anna Ferrulli, Estelle Barbier, Robert Hitzemann, Vanessa A. Jimenez, Elie Aoun, Kathleen A. Grant, N. A. R. Walter, George F. Koob, Mary R. Lee |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male principal component analysis Craving Self Administration chemistry.chemical_compound 0302 clinical medicine Mineralocorticoid receptor Receptor Prefrontal cortex Aldosterone Central nucleus of the amygdala Amygdala animal models 3. Good health Psychiatry and Mental health Alcoholism alcoholic patients Psychopharmacology medicine.symptom Psychology Neurovetenskaper Preliminary Data Adult medicine.medical_specialty Alcohol Drinking medicine.drug_class Settore MED/12 - GASTROENTEROLOGIA Prefrontal Cortex Article 03 medical and health sciences Cellular and Molecular Neuroscience alcohol use disorders monkeys Internal medicine Mineralocorticoids medicine Animals Cytochrome P-450 CYP11B2 Humans Rats Wistar Molecular Biology mineralocorticoid receptor Ethanol Neurosciences Macaca mulatta Rats Disease Models Animal 030104 developmental biology Endocrinology Receptors Mineralocorticoid chemistry Mineralocorticoid alcohol craving 030217 neurology & neurosurgery |
| Zdroj: | Molecular psychiatry |
| Popis: | 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. 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] |
| Databáze: | OpenAIRE |
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