Microglia Control Escalation of Drinking in Alcohol-Dependent Mice: Genomic and Synaptic Drivers.

Alcohol Drinking Alcoholism / genetics Animals Ethanol Genomics Mice Microglia Synaptic Transmission
Alcohol Electrophysiology Ethanol dependence Microglia PLX5622 Transcriptome

Journal

Biological psychiatry
ISSN: 1873-2402
Titre abrégé: Biol Psychiatry
Pays: United States
ID NLM: 0213264

Informations de publication

Date de publication:
15 12 2020
Historique:
received: 09 02 2020
revised: 10 04 2020
accepted: 06 05 2020
pubmed: 19 7 2020
medline: 9 3 2021
entrez: 19 7 2020
Statut: ppublish

Résumé

Microglia, the primary immune cells of the brain, are implicated in alcohol use disorder. However, it is not known if microglial activation contributes to the transition from alcohol use to alcohol use disorder or is a consequence of alcohol intake. We investigated the role of microglia in a mouse model of alcohol dependence using a colony stimulating factor 1 receptor inhibitor (PLX5622) to deplete microglia and a chronic intermittent ethanol vapor two-bottle choice drinking procedure. Additionally, we examined anxiety-like behavior during withdrawal. We then analyzed synaptic neuroadaptations in the central nucleus of the amygdala (CeA) and gene expression changes in the medial prefrontal cortex and CeA from the same animals used for behavioral studies. PLX5622 prevented escalations in voluntary alcohol intake and decreased anxiety-like behavior associated with alcohol dependence. PLX5622 also reversed expression changes in inflammatory-related genes and glutamatergic and GABAergic (gamma-aminobutyric acidergic) genes in the medial prefrontal cortex and CeA. At the cellular level in these animals, microglia depletion reduced inhibitory GABA Our multifaceted approach is the first to link microglia to the molecular, cellular, and behavioral changes associated with the development of alcohol dependence, suggesting that microglia may also be critical for the development and progression of alcohol use disorder.

Sections du résumé

BACKGROUND
Microglia, the primary immune cells of the brain, are implicated in alcohol use disorder. However, it is not known if microglial activation contributes to the transition from alcohol use to alcohol use disorder or is a consequence of alcohol intake.
METHODS
We investigated the role of microglia in a mouse model of alcohol dependence using a colony stimulating factor 1 receptor inhibitor (PLX5622) to deplete microglia and a chronic intermittent ethanol vapor two-bottle choice drinking procedure. Additionally, we examined anxiety-like behavior during withdrawal. We then analyzed synaptic neuroadaptations in the central nucleus of the amygdala (CeA) and gene expression changes in the medial prefrontal cortex and CeA from the same animals used for behavioral studies.
RESULTS
PLX5622 prevented escalations in voluntary alcohol intake and decreased anxiety-like behavior associated with alcohol dependence. PLX5622 also reversed expression changes in inflammatory-related genes and glutamatergic and GABAergic (gamma-aminobutyric acidergic) genes in the medial prefrontal cortex and CeA. At the cellular level in these animals, microglia depletion reduced inhibitory GABA
CONCLUSIONS
Our multifaceted approach is the first to link microglia to the molecular, cellular, and behavioral changes associated with the development of alcohol dependence, suggesting that microglia may also be critical for the development and progression of alcohol use disorder.

Identifiants

DOI: 10.1016/j.biopsych.2020.05.011 PMID: 32680583 PMC: PMC7674270
pubmed: 32680583
pii: S0006-3223(20)31598-5
doi: 10.1016/j.biopsych.2020.05.011
pmc: PMC7674270
mid: NIHMS1595811
pii:
doi:

Substances chimiques

Ethanol 3K9958V90M

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

910-921

Subventions

Organisme : NIAAA NIH HHS
ID : R01 AA027700
Pays : United States
Organisme : NIAAA NIH HHS
ID : U01 AA013498
Pays : United States
Organisme : NIAAA NIH HHS
ID : R37 AA006399
Pays : United States
Organisme : NIAAA NIH HHS
ID : R00 AA025408
Pays : United States
Organisme : NIAAA NIH HHS
ID : T32 AA007456
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA017447
Pays : United States
Organisme : NIAAA NIH HHS
ID : P01 AA020683
Pays : United States
Organisme : NIAAA NIH HHS
ID : P60 AA006420
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA021491
Pays : United States
Organisme : NIAAA NIH HHS
ID : U01 AA020926
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA012404
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA006399
Pays : United States
Organisme : NIAAA NIH HHS
ID : U01 AA013520
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA017477
Pays : United States
Organisme : NIAAA NIH HHS
ID : K99 AA025408
Pays : United States
Organisme : NIAAA NIH HHS
ID : F31 AA025499
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA015566
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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Auteurs

Anna S Warden (AS)

Waggoner Center for Alcoholism and Addiction Research, University of Texas at Austin, Austin, Texas; Institute for Neuroscience, University of Texas at Austin, Austin, Texas.

Sarah A Wolfe (SA)

Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute, La Jolla, California.

Sophia Khom (S)

Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute, La Jolla, California.

Florence P Varodayan (FP)

Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute, La Jolla, California.

Reesha R Patel (RR)

Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute, La Jolla, California.

Michael Q Steinman (MQ)

Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute, La Jolla, California.

Michal Bajo (M)

Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute, La Jolla, California.

Sarah E Montgomery (SE)

Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute, La Jolla, California.

Roman Vlkolinsky (R)

Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute, La Jolla, California.

Tali Nadav (T)

Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute, La Jolla, California.

Ilham Polis (I)

Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute, La Jolla, California.

Amanda J Roberts (AJ)

Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute, La Jolla, California.

R Dayne Mayfield (RD)

Waggoner Center for Alcoholism and Addiction Research, University of Texas at Austin, Austin, Texas; Institute for Neuroscience, University of Texas at Austin, Austin, Texas.

R Adron Harris (RA)

Waggoner Center for Alcoholism and Addiction Research, University of Texas at Austin, Austin, Texas; Institute for Neuroscience, University of Texas at Austin, Austin, Texas.

Marisa Roberto (M)

Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute, La Jolla, California. Electronic address: mroberto@scripps.edu.

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Classifications MeSH

questionsmedicales.fr › Comportement et mécanismes comportementaux › Comportement › Comportement dipsique › Consommation d'alcool › Microglia Control Escalation of Drinking in...
questionsmedicales.fr › Troubles mentaux › Troubles liés à une substance › Troubles liés à l'alcool › Alcoolisme › Microglia Control Escalation of Drinking in...
questionsmedicales.fr › Eucaryotes › Animaux › Microglia Control Escalation of Drinking in...
questionsmedicales.fr › Composés chimiques organiques › Alcools › Éthanol › Microglia Control Escalation of Drinking in...
questionsmedicales.fr › Disciplines des sciences naturelles › Disciplines des sciences biologiques › Biologie › Génétique › Génomique › Microglia Control Escalation of Drinking in...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Microglia Control Escalation of Drinking in...
questionsmedicales.fr › Cellules › Névroglie › Microglie › Microglia Control Escalation of Drinking in...
questionsmedicales.fr › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système nerveux › Transmission synaptique › Microglia Control Escalation of Drinking in...