Social isolation-related depression accelerates ethanol intake via microglia-derived neuroinflammation.
Sci Adv
; 7(45): eabj3400, 2021 Nov 05.
Article
en En
| MEDLINE
| ID: mdl-34739315
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Aspecto:
Determinantes_sociais_saude
Idioma:
En
Revista:
Sci Adv
Año:
2021
Tipo del documento:
Article