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.