Abstract: Objective To investigate whether the effects of venlafaxine on major depression disorder is associated with ankyrin G. Methods Breed Synapsin-Cre1 and Ankyrin3-floxed mice (Ank3 cKO mice). Ank3 cKO mice and wild type mice were randomly divided into model and control groups. All mice in model group and control group were orally administrated with venlafaxine(1 g/L) or the solvent(normal saline, NS) with the volume of 200 μL,respectively. Depression-related behaviors were examined by sucrose preference test (SPT) and Y maze test. The level of ankyrin G and PSD95 in the cortex of four groups were detected by Western blot. The level of ankyrin G and MAP2 in the in hippocampus of four groups were detected by immunohistochemistry method. ResultsCompared with wt-saline group, the cKO mice in saline showed a significantly decreased preference of sucrose (P＜0.001) and low spontaneous alteration(P＜0.05). Compared with cKO control ones, the venlafaxine model cKO mice showed remarkably increased preference of sucrose(P＜0.001) and more spontaneous alteration(P＜0.05). The level of ankyrin G and PSD-95 in the cortex of venlafaxine cKO mice was much higher than that in control mice(P＜0.01)The level of ankyrin G and MAP2 in the hippocampus of venlafaxine cKO mice were much higher than those of control mice(P＜0.05). Conclusions Venlafaxine alleviates the depression symptoms caused by knocking down Ank3. The mechanism of depression treatment by venlafaxine is potentially associated with levitating ankyrin G level in prefrontal cortex and hippocampus.

Key words: major depression disorder, venlafaxine, ankyrin