Abstract: Objective To investigate the effects of vortioxetine on cAMP/CREB/BDNF signal pathway. Methods Forty Kunming
mice were randomized into control group and chronic unpredictable mild stress (CUMS) group. After establishment of depressive
models verified by sucrose preference test, the mice in CUMS group were divided into model group, fluoxetine group and
vortioxetine group. The antidepressive effect of vortioxetine was analyzed by tail suspension test, forced swim test and open
field test. The levels of cAMP were detected using a commercial ELISA kit, and the expressions of pCREB and brain-derived
neurotrophic factor (BDNF) were evaluated with Western blotting. Results Vortioxetine significantly shortened the immobility
time of the depressive mice in tail suspension test and forced swim test without affecting the locomotor activity of the mice in
open fields, suggesting the antidepressive effect of against depression in mice. Vortioxetine significantly increased the levels of
cAMP and promoted the expression of pCREB and BDNF in the hippocampus of the mice (P<0.01). Conclusion Vortioxetine
improves the behaviors of mice with depression possibly by affecting the cAMP/CREB/BDNF signal pathway.