Mesocortical BDNF signaling mediates antidepressive-like effects of lithium.

ABSTRACT: Lithium has been used to treat major depressive disorder, yet the neural circuit mechanisms underlying this therapeutic effect remain unknown. Here, we demonstrated that the ventral tegmental area (VTA) dopamine (DA) neurons that project to the medial prefrontal cortex (mPFC), but not to nucleus accumbens (NAc), contributed to the antidepressive-like effects of lithium. Projection-specific electrophysiological recordings revealed that high concentrations of lithium increased firing rates in mPFC-, but not NAc-, projecting VTA DA neurons in mice treated with chronic unpredictable mild stress (CMS). In parallel, chronic administration of high-dose lithium in CMS mice restored the firing properties of mPFC-projecting DA neurons, and also rescued CMS-induced depressive-like behaviors. Neverthe

SUBMITTER: Liu D 

PROVIDER: S-EPMC7360776 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature