Social isolation-related depression accelerates ethanol intake via microglia-derived neuroinflammation

Social isolation is common in modern society and is a contributor to depressive disorders. People with depression are highly vulnerable to alcohol use, and abusive alcohol consumption is a well-known obstacle to treating depressive disorders. Using a mouse model involving isolation stress (IS) and/o...

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Bibliographic Details
Published in:Science advances 2021-11, Vol.7 (45), p.eabj3400-eabj3400
Main Authors: Lee, Jin-Seok, Lee, Sung-Bae, Kim, Dong-Woon, Shin, Nara, Jeong, Seon-Ju, Yang, Chae-Ha, Son, Chang-Gue
Format: Article
Language:English
Subjects:
Life Sciences
Neuroscience
SciAdv r-articles
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Summary:Social isolation is common in modern society and is a contributor to depressive disorders. People with depression are highly vulnerable to alcohol use, and abusive alcohol consumption is a well-known obstacle to treating depressive disorders. Using a mouse model involving isolation stress (IS) and/or ethanol intake, we investigated the mutual influence between IS-derived depressive and ethanol-seeking behaviors along with the underlying mechanisms. IS increased ethanol craving, which robustly exacerbated depressive-like behaviors. Ethanol intake activated the mesolimbic dopaminergic system, as evidenced by dopamine/tyrosine hydroxylase double-positive signals in the ventral tegmental area and c-Fos activity in the nucleus accumbens. IS-induced ethanol intake also reduced serotonergic activity, via microglial hyperactivation in raphe nuclei, that was notably attenuated by a microglial inhibitor (minocycline). Our study demonstrated that microglial activation is a key mediator in the vicious cycle between depression and alcohol consumption. We also propose that dopaminergic reward might be involved in this pathogenicity.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.abj3400