Chronic Ethanol Consumption Alters Glucocorticoid Receptor Isoform Expression in Stress Neurocircuits and Mesocorticolimbic Brain Regions of Alcohol-Preferring Rats.
GRα
GRβ
P rats
ethanol
nucleus accumbens
Journal
Neuroscience
ISSN: 1873-7544
Titre abrégé: Neuroscience
Pays: United States
ID NLM: 7605074
Informations de publication
Date de publication:
15 06 2020
15 06 2020
Historique:
received:
02
12
2019
revised:
20
04
2020
accepted:
21
04
2020
pubmed:
1
5
2020
medline:
15
5
2021
entrez:
1
5
2020
Statut:
ppublish
Résumé
Evidence suggests the hypothalamic-pituitary-adrenal (HPA) axis is involved in Alcohol Use Disorders (AUDs), which might be mediated by an imbalance of glucocorticoid receptor (GR), GRα and GRβ, activity. GRβ antagonizes the GRα isoform to cause glucocorticoid (GC) resistance. In the present study, we aimed to investigate the effects of chronic continuous free-choice access to ethanol on GR isoform expression in subregions of the mesocorticolimbic reward circuit. Adult male alcohol-preferring (P) rats had concurrent access to 15% and 30% ethanol solutions, with ad lib access to lab chow and water, for six weeks. Quantitative Real-time PCR (RT-PCR) analysis showed that chronic ethanol consumption reduced GRα expression in the nucleus accumbens shell (NAcsh) and hippocampus, whereas ethanol drinking reduced GRβ in the nucleus accumbens core (NAcc), prefrontal cortex (PFC), and hippocampus. An inhibitor of GRα, microRNA-124-3p (miR124-3p) was significantly higher in the NAcsh, and GC-induced gene, GILZ, as a measure of GC-responsiveness, was significantly lower. These were not changed in the NAcc. Likewise, genes associated with HPA axis activity were not significantly changed by ethanol drinking [i.e., corticotrophin-releasing hormone (Crh), adrenocorticotrophic hormone (Acth), and proopiomelanocortin (Pomc)] in these brain regions. Serum corticosterone levels were not changed by ethanol drinking. These data indicate that the expression of GRα and GRβ isoforms are differentially affected by ethanol drinking despite HPA-associated peptides remaining unchanged, at least at the time of tissue harvesting. Moreover, the results suggest that GR changes may stem from ethanol-induced GC-resistance in the NAcsh. These findings confirm a role for stress in high ethanol drinking, with GRα and GRβ implicated as targets for the treatment of AUDs.
Identifiants
pubmed: 32353460
pii: S0306-4522(20)30265-7
doi: 10.1016/j.neuroscience.2020.04.033
pmc: PMC7718101
mid: NIHMS1650270
pii:
doi:
Substances chimiques
Glucocorticoids
0
MIRN124 microRNA, rat
0
MicroRNAs
0
Protein Isoforms
0
RNA, Messenger
0
Receptors, Glucocorticoid
0
Ethanol
3K9958V90M
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
107-116Subventions
Organisme : NIAAA NIH HHS
ID : R01 AA019458
Pays : United States
Organisme : NIAAA NIH HHS
ID : P60 AA007611
Pays : United States
Organisme : NHLBI NIH HHS
ID : K01 HL125445
Pays : United States
Organisme : NIAAA NIH HHS
ID : U24 AA015512
Pays : United States
Organisme : NIAAA NIH HHS
ID : U01 AA013522
Pays : United States
Organisme : NIAAA NIH HHS
ID : U24 AA013522
Pays : United States
Informations de copyright
Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.
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