Vortioxetine administration attenuates cognitive and synaptic deficits in 5×FAD mice.

RATIONALE AND OBJECTIVE: Vortioxetine has been reported to exhibit a variety of neurobiological functions and neuroprotective effects. In the present study, we aimed to investigate the effects of vortioxetine on cognitive performance in a transgenic mouse model of Alzheimer's disease (AD). METHODS: We administered vortioxetine (10 mg/kg, i.p., every day, for approximately 6 weeks), which acts on multiple 5-serotonin (5-HT) receptors, to 3.5-month-old 5×FAD mice. Subsequently, we used the open field (OF) test to detect anxiety-like behavior in the mice. The novel object recognition (NOR) test and Morris water maze (MWM) were used to assess the cognitive states of the 5×FAD mice. We also measured the levels of insoluble amyloid plaques and soluble ß-amyloid (Aß) plaques. Finally, we explored the expression levels of postsynaptic density protein 95 (PSD95), synaptophysin (SYP), and synaptotagmin-1 (SYT1) in the hippocampus of the mice. RESULTS: The administration of vortioxetine effectively reversed the reduction in anxiety-type behaviors in 5×FAD mice and improved the impairment in recognition memory and spatial reference memory. However, we did not find that vortioxetine decreased or delayed the formation of amyloid plaques or Aß. Interestingly, we found a significant increase in the expression levels of PSD95, SYP, and SYT1 in the 5×FAD mice after vortioxetine treatment compared with the control group. CONCLUSION: These results demonstrate that vortioxetine may improve cognitive impairment in 5×FAD mice. The role in cognitive improvement may be related to the beneficial effects of vortioxetine on synaptic function.