The contribution of oxidative stress has been described in numerous studies as one of the main pathways involved in the pathophysiology of anxiety and its comorbidities, such as chronic pain. Therefore, in this study, we investigated the anxiolytic-like, antiallodynic, and anti-hyperalgesic effects of 3,5-dimethyl-1-phenyl-4-(phenylselanyl)-1H-pyrazole (SePy) in response to acute restraint stress (ARS) in mice through the modulation of oxidative stress and neuroendocrine responses. Mice were restrained for 2 h followed by SePy (1 or 10 mg/kg, intragastrically) treatment. Behavioral, and biochemical tests were performed after further 30 min. The treatment with SePy reversed (i) the decreased time spent and the number of entries in the open arms of the elevated plus-maze apparatus, (ii) the decreased time spent in the central zone of the open field test and the increased number of grooming, (iii) the increased number of marbles buried, (iv) the increased response frequency of Von Frey Hair stimulation, and (v) the decreased latency time to nociceptive response in the hot plate test stress induced by ARS. Biochemically, SePy reversed ARS-induced increased levels of plasma corticosterone, and reversed the ARS-induced alterations in the levels of reactive species, lipid peroxidation, and superoxide dismutase and catalase activities in the prefrontal cortices and hippocampi of mice. Moreover, a molecular docking approach suggested that SePy may interact with the active site of the glucocorticoid receptor. Altogether, these results indicate that SePy attenuated anxiolytic-like behavior, hyperalgesia, and mechanical allodynia while modulating oxidative stress and neuroendocrine responses in stressed mice.

氧化应激的贡献已在许多研究中被描述为参与焦虑及其合并症（如慢性疼痛）病理生理学的主要途径之一。因此，在本研究中，我们研究了 3,5-二甲基-1-苯基-4-(苯基硒基)-1H-吡唑 (SePy) 对急性束缚应激的抗焦虑样、抗异常性疼痛和抗痛觉过敏作用。 ARS) 在小鼠中通过调节氧化应激和神经内分泌反应。小鼠被限制 2 小时，然后进行 SePy（1 或 10 毫克/千克，灌胃）治疗。再过 30 分钟后进行行为和生化测试。用 SePy 处理逆转了 (i) 在高架十字迷宫装置的开放臂中花费的时间和进入次数的减少，(ii) 在露天试验中心区花费的时间减少，梳理次数增加，(iii) 埋藏的弹珠数量增加，(iv) 冯弗雷毛发刺激的响应频率增加，以及 (v)在 ARS 诱导的热板测试应力中，到伤害性反应的潜伏期减少。在生化方面，SePy 逆转了 ARS 诱导的血浆皮质酮水平升高，并逆转了 ARS 诱导的小鼠前额叶皮质和海马中活性物质、脂质过氧化、超氧化物歧化酶和过氧化氢酶活性水平的改变。此外，分子对接方法表明，SePy 可能与糖皮质激素受体的活性位点相互作用。总之，这些结果表明 SePy 减弱了抗焦虑样行为、痛觉过敏、