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.

在过去的几十年中，含硒化合物由于其各种生物学和药理特性而受到越来越多的关注。在本研究中，我们研究了3-[（4-甲氧基苯基）癸酰基] -2-苯基咪唑并[1,2-a]吡啶（MPI; 1，10或50 mg / kg，ig）对急性抑制作用的影响应激（ARS）诱导的小鼠抑郁和焦虑样行为及其潜在的作用机制。我们使用开放式测试，强迫游泳测试和飞溅测试来评估抑郁样行为，并使用大理石掩埋法和高架迷宫测试来评估焦虑样行为。我们发现，MPI在所有行为测试中均能减弱ARS引起的抑郁和焦虑样行为，而对非应激小鼠没有影响。MPI可防止促炎性细胞因子吲哚胺2（Indoleamine-2）的增加，通过激活的B细胞（NF-κB）的规范核因子κ-轻链增强剂下调脑组织中的3-双加氧酶（IDO）和诱导型一氧化氮合酶（iNOS）的表达。此外，MPI预防了ARS诱导的脑源性神经营养因子（BDNF）的下调，增加了小鼠前额叶皮层和海马中活性氧/氮物质的产生以及脂质过氧化作用。此外，MPI阻止了前额叶皮层和海马中糖皮质激素受体的下调，并减少了应激小鼠中皮质酮的循环水平升高。这些结果表明，MPI具有抗抑郁和抗焦虑的特性，其作用可能与前额叶皮层和海马的生物学变化有关。