AI Article Synopsis
- Microglia, the immune cells in the brain, are suspected to play a role in alcohol use disorder, but it's unclear if their activation is a cause or a result of alcohol consumption.
- In a mouse study, researchers used a microglial inhibitor to explore its effects on alcohol dependence and found that depleting microglia reduced alcohol intake and anxiety during withdrawal, while also reversing gene expression changes related to inflammation and neurotransmission.
- This study is significant because it establishes a connection between microglia and the biological and behavioral factors involved in developing alcohol use disorder, suggesting that targeting microglia could be important for treatment strategies.
Article Abstract
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 and excitatory glutamate receptor-mediated synaptic transmission in the CeA, supporting the hypothesis that microglia regulate dependence-induced changes in neuronal function.
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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674270 | PMC |
| http://dx.doi.org/10.1016/j.biopsych.2020.05.011 | DOI Listing |
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