Chronic Fluoxetine Treatment Reverses Depressive-like Behaviors in Mice via Enhancing Neuroplasticity

Objectives: Depression remains a refractory psychiatric disorder. Fluoxetine is a preferred class of antidepressant medication due to restrain retaking of biogenic monoamines. There was a new mechanism discovery that neuroplasticity was considered to underlie clinical antidepressant effects. However, reports display that fluoxetine’s actions on neuroplasticity still remain controversial. This study investigates fluoxetine’s role in the impact of synaptic function and morphology by different durations of fluoxetine treatment and the possible mechanisms involved. Materials and Methods: The chronic depression mice model was established by using the 7-week-old male C57BL/6 mice. Fluoxetine 10 mg/kg was treated for 7 days and 14 days. The depression-like behaviors were assessed using the tail-suspension test, forced swim test, sucrose preference, and open-field tests. Nissl staining was applied to assess hippocampus formation. Immunofluorescence and Golgi staining were used to investigate synaptic function and morphology. The hippocampal protein expression of SYP was examined using Western blotting. Results: We found that fluoxetine treatment for 2 weeks, as opposed to just 1 week, significantly alleviated symptoms of behavioral despair, anhedonia, and anxiety in the depressive mice. Furthermore, both 7- and 14-day fluoxetine administrations resulted in reduced impairment of hippocampal neurons and a tendency to increase the dendritic spine numbers in the context of depression. Additionally, only the 14-day fluoxetine treatment promoted the expression of SYP in the hippocampus. Conclusion: Chronic administration of fluoxetine significantly reduced depressive and anxiety-like behaviors and hippocampal impairment and enhanced synaptic plasticity in mice.