Silymarin Potentiates the Effect of Buspirone on Anxiety and Depressive-Like Behaviors Induced by Chronic Restraint Stress in Male Mice

Abstract

Background: Stress and its complications such as anxiety and depression continue to be regarded as health issues in human societies. Therefore, an effective treatment strategy is highly valued for dealing with stress and related disorders. In spite of studies suggesting the neuroprotective effects of silymarin and buspirone alone, the combined effects of these treatments on chronic stress have not been elucidated yet. Thus, this study aimed to investigate the effect of silymarin and buspirone (alone or in combination) on anxiety and depressive-like behaviors and to evaluate corticosterone levels in a mice model of chronic restraint stress (RS). Methods: This study was conducted on seventy-two male BALB/c mice which were allocated in six equal groups. The animals were exposed to chronic RS (2 hours/day for 14 days) to induce a depressive-like model. An elevated plus maze (EPM) was performed to assess anxiety, while a tail suspension test (TST) was implemented to evaluate depressive-like behavior. Furthermore, the serum levels of corticosterone were measured by the enzyme-linked immunosorbent assay method. Results: Our data demonstrated that exposure to RS resulted in prolonged immobility in the TST and reduced time spent in the open arms of the EPM test. Buspirone perorally (5 mg/kg, PO) alone and combined with silymarin (200 mg/kg, PO) increased time spent in the open arms of the EPM apparatus while attenuating immobility time in TST. There was a significant decrease in the blood corticosterone level of buspirone and silymarin co-treated animals. Conclusion: These findings indicated that silymarin potentiates the beneficial effect of buspirone against chronic RS-induced anxiety and depressive-like behaviors in mice by lowering corticosterone serum levels. In this regard, further investigations should be undertaken to clarify the exact mechanism of the observed effects.