Fluoxetine mitigates depressive-like behaviors in mice via anti-inflammation and enhancing neuroplasticity.

Neuroplasticity and inflammation represent a common final pathway for effective antidepressant treatment. SSRIs are the most commonly prescribed medications for depression and have demonstrated efficacy in reducing depressive symptoms. However, the precise impact of SSRIs on neuroplasticity and inflammation remains unclear. In this study, we aimed to investigate the influence of long-term treatment with SSRIs on hippocampal neuron, inflammation, synaptic function and morphology. Our findings revealed that fluoxetine treatment significantly alleviated behavioral despair, anhedonia, and anxiety in reserpine-treated mice. Moreover, fluoxetine mitigated hippocampal neuron impairment, inhibited inflammatory release, and increased the expression of synaptic proteins markers (SYP and PSD95) in mice. Notably, fluoxetine also suppressed reserpine-induced synapse loss in the hippocampus. Based on these results, fluoxetine has been demonstrated effectively to ameliorate depressive mood and cognitive dysfunction, possibly through the enhancement of synaptic plasticity. Overall, our study contributes to a further understanding of the mechanisms underlying the therapeutic effects of fluoxetine and its potential role in improving depressive symptoms and cognitive impairments.

Repeated reserpine treatment induces depressive-like behaviors accompanied with hippocampal impairment and synapse deficit in mice.

Depression remains a significant public health concern, and current animal models of depression are limited in their ability to accurately mimic human depression. However, studying the new development of antidepressants requires the use of progressive animal models. In this study, the mice were exposed to a low dose of reserpine (0.5 mg/kg) once daily for 14 days, followed by a 14-day period to allow for the development of spontaneous depression. We have successfully established a repeated reserpine-induced depressive animal model, which was characterized by emotional symptoms (anhedonia), cognitive symptoms, and psychomotor agitation or retardation. Our study demonstrated that repeated treatment with low-dose reserpine increased immobility time in the TST and FST. It also decreased the sucrose consumption ratio and induced anxiety-like behaviors. These anxiety-like behaviors were evidenced by decreased time spent in the center zone, longer first latency to center zone, and fewer entries into the center zone in the open field test. These findings support the utility of the low-dose reserpine repeated injection animal model for studying the pathogenesis of depression and the development of novel antidepressant treatments. Additionally, this study provides valuable insights into the potential of low-dose reserpine as a tool for modeling chronic depression in animals. Furthermore, our findings suggest that prolonged low-dose reserpine treatment could result in chronic depression. These findings have significant implications for the use of reserpine as a therapeutic agent for various conditions and emphasize the importance of closely monitoring patients' mental health.