7,8-Dihydroxyflavone reverses the depressive symptoms in mouse chronic mild stress

•7,8-DHF produced antidepressant-like effects in CMS mice.•7,8-DHF promoted the expression of synaptic proteins.•K252a pretreatment blocked the effects of 7,8-DHF. 7,8-Dihydroxyflavone (7,8-DHF) is a naturally-occurring flavone which possesses good bioavailability. Due to its ability to cross the blood-brain barrier, previous studies have demonstrated that 7,8-DHF was a potent tropomyosin-related kinase B (TrkB) agonist, and produced antidepressant-like effects in mouse forced swimming test and tail suspension test. However, it has not been evaluated in chronic mild stress (CMS), a classical depression model modulating the processes of major depression in human. In the present study, we not only evaluated the depressive-like behaviors, but also measured the key proteins of TrkB signaling in mice exposed to CMS. Our results firstly found that long term but not single injection of 7,8-DHF restored the depressive-like behaviors in sucrose preference test and novelty suppressed feeding test. In addition, 7,8-DHF not only increased TrkB phosphorylation and brain-derived neurotrophic factor (BDNF) levels, but also activated the expression of TrkB downstream synaptic proteins such as PSD95 and synaptophysin. Furthermore, the TrkB antagonist K252a blocked the antidepressant-like effects of 7,8-DHF. In summary, the present results demonstrated that chronic 7,8-DHF treatment exerted significant antidepressant-like effects, which were likely attributed to regulating TrkB signaling and thus promoting synaptic protein expression.