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

Biological Psychiatry
Anna S WardenMarisa Roberto

Abstract

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 GABAA and excitatory glutamate receptor-mediated synaptic transmission in the CeA, supporti...Continue Reading

Citations

Dec 29, 2020·Neurochemistry International·Samuel DeurveilherKazue Semba
Nov 10, 2020·Alcoholism, Clinical and Experimental Research·Hui Peng, Kimberly Nixon
Dec 16, 2020·Antioxidants·Muhammad Syahreel Azhad Sha'fieSharifah Alawieyah Syed Mortadza
Feb 22, 2021·Journal of Neuroscience Research·Fulton T CrewsLeon G Coleman
Jun 16, 2021·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Courtney E KingHoward C Becker
Jul 14, 2021·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Yosef AvchalumovChitra D Mandyam
Aug 4, 2021·Brain, Behavior, and Immunity·Lindsay R MeredithLara A Ray
Sep 7, 2021·Alcoholism, Clinical and Experimental Research·Jennifer K MelbourneKimberly Nixon

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