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首页> 外文期刊>Physiological Reports >Effects of short‐term clomipramine on anxiety‐like behavior, cellular metabolism, and oxidative stress in primary fibroblast cells of male and female rats
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Effects of short‐term clomipramine on anxiety‐like behavior, cellular metabolism, and oxidative stress in primary fibroblast cells of male and female rats

机译：短期氯米帕明对雄性和雌性大鼠原代成纤维细胞焦虑样行为，细胞代谢和氧化应激的影响

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Anxiety is the most prevalent mental disorder among adults in the United States and females tend to have significantly higher rates of anxiety compared with men. Common treatments for anxiety include usage of selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants, however, sex differences in the efficacy of these drugs exist. In this study, we were interested in determining if acutely manipulating serotonin mechanisms at the whole‐animal level affects cellular metabolism and oxidative stress in primary fibroblast cells from clomipramine‐treated Sprague‐Dawley rats. Our groups included a female and male control group that was injected with a saline solution, a female and male group that was injected with a low dosage of clomipramine, and a female and male group of rats that were injected with a high dosage of clomipramine. We then compared cellular oxygen consumption rates, rates of glycolysis and oxidative stress parameters in primary fibroblasts grown from each of the groups described above. We found that clomipramine‐treated rats had significantly lower rates of glycolysis and glycolytic capacity, regardless of sex. Coupling efficiency was significantly higher in male rats compared with female rats across treatment groups. Our data suggest that in female rats reduced glutathione (GSH) is nonsignificantly reduced, yet lipid peroxidation (LPO) damage still accumulates, meaning that enzymatic antioxidants may be acting to reduce any continual increases in LPO damage. This is a metabolically costly process that may be happening because of our drug treatments. Our results provide further evidence of sex differences in the behavioral and metabolic responses to short‐term clomipramine treatment. Continued investigation into these sex differences may reveal their potential for improving our understanding of how different therapeutic interventions may be better suited for treating males and females.
机译：在美国成年人中，焦虑症是最普遍的精神障碍，而与男性相比，女性的焦虑症倾向明显更高。焦虑症的常见治疗方法包括使用选择性5-羟色胺再摄取抑制剂（SSRI）和三环抗抑郁药，但是，这些药物的疗效存在性别差异。在这项研究中，我们感兴趣的是确定在整个动物水平上急性操作血清素的机制是否会影响氯米帕明治疗的Sprague-Dawley大鼠的原代成纤维细胞的细胞代谢和氧化应激。我们的组包括雌性和雄性对照组，分别注射盐溶液，雌性和雄性组，注射低剂量的氯米帕明，以及雌性和雄性大鼠组，注射高剂量的氯米帕明。然后，我们比较了从上述各组生长的初级成纤维细胞中的细胞耗氧率，糖酵解速率和氧化应激参数。我们发现，不论性别，使用氯米帕明治疗的大鼠的糖酵解率和糖酵解能力均显着降低。在治疗组中，雄性大鼠的耦合效率明显高于雌性大鼠。我们的数据表明，在雌性大鼠中，还原型谷胱甘肽（GSH）的减少没有明显减少，但脂质过氧化（LPO）损伤仍在累积，这意味着酶促抗氧化剂可能会减少LPO损伤的任何持续增加。由于我们的药物治疗，这可能是一个代谢代价高昂的过程。我们的结果为短期氯米帕明治疗的行为和代谢反应中的性别差异提供了进一步的证据。对这些性别差异的持续调查可能显示出它们有潜力增进我们对不同治疗干预措施可能更适合于治疗男性和女性的理解。

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