Effects of a selanylimidazopyridine on the acute restraint stress-induced depressive- and anxiety-like behaviors and biological changes in mice

In the last decades, selenium-containing compounds have received increasing attention due to their various biological and pharmacological properties. In the present study, we investigated the effects of 3-[(4-methoxyphenyl) selanyl]-2-phenylimidazo[1,2-a] pyridine (MPI; 1, 10 or 50 mg/kg, i.g.) on the acute restraint stress (ARS)-induced depressive- and anxiety-like behaviors in mice and its underlying mechanism of action. We used the open filed test, forced swimming test, and splash test to evaluate depressive-like behavior, and marble burying and elevated plus maze test to measure anxiety-like behavior. We found that MPI attenuated ARS-induced depressive- and anxiety-like behaviors in all behavioral tests, without having an effect in non-stressed mice. MPI prevented the increased in pro-inflammatory cytokines, indoleamine-2,3-dioxygenase (IDO) and inducible nitric oxide synthase (iNOS) expression in brain structures via canonical nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) down-regulation. Additionally, MPI prevented ARS-induced downregulation of brain-derived neurotrophic factor (BDNF), increased reactive oxygen/nitrogen species generation and lipid peroxidation in prefrontal cortex and hippocampus of mice. In addition, MPI blocked the downregulation of glucocorticoid receptors in the prefrontal cortex and hippocampus and reduced the increased circulating level of corticosterone in stressed mice. These results suggested that MPI showed antidepressant- and anxiolytic-like properties and the effects might be associated with the biological changes in the prefrontal cortex and hippocampus.