期刊
BIOLOGICAL PSYCHIATRY
卷 88, 期 12, 页码 910-921出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2020.05.011
关键词
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资金
- National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism [U01 AA020926, U01 AA013498, P60 AA006420, R01 AA015566, AA017477, R01 AA027700, R01 AA021491, T32 AA007456, P01 AA020683, R01 AA012404, F31 AA025499, K99 AA025408]
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(A) 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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