Diosgenin via NMDA Receptor Exerted Anxiolytic-like Effect on Maternally Separated Mice

Background and aim: Anxiety is one of the most common psychiatric disorders that lead to the disruption of daily life and also the quality of life. Routine medications have many side effects and cause physical dependence and psychosocial addiction. Diosgenin is a phytosteroid found in a number of herbs. The present study aimed to investigate the anxiolytic-like effect of diosgenin in the maternal separation model in male mice focusing on the role of NMDA receptors. Materials and Methods: Maternal separation (MS) paradigm was performed daily (3 h) from postnatal day (PND) 2-14. Male mice were treated with different doses of diosgenin to find effective and sub-effective doses. In the next step, mice were treated with an effective dose of diosgenin plus NMDA and or a sub-effective dose of diosgenin plus ketamine (NMDA antagonist). Valid behavioral tests for the evaluation of anxiety-like behavior were performed. Then, mice were euthanized, the hippocampus was dissected out and gene expression of NMDA receptors (NR2a and NR2b subunits) was assessed. Results: MS provokes anxiety-like behaviors in the open field test (OFT) and elevated plus maze (EPM) test. Diosgenin significantly mitigated the negative effects of MS. Co-administration of NMDA attenuated anxiolyticlike effect of the effective dose of diosgenin, while ketamine potentiated the anxiolytic effect of sub-effective dose of diosgenin. Furthermore, MS increased the expression of the NMDA receptor in the hippocampus which to some extent modulated with diosgenin. Conclusion: Diosignin has an anxiolytic-like effect on MS mice which at least, in part, mediated through NMDA receptors.