Rapid-onset antidepressant-like effect of sub-therapeutic dose of iron in combination with citalopram or imipramine in mice

In this study, we hypothesize that sub-therapeutic dose of iron combined with classical antidepressants such as citalopram and imipramine will produce rapid-onset antidepressant-like effect in mice. First, the study assessed the antidepressant effects of iron, citalopram or imipramine alone in murine behavioral models. Behavioral tests such as forced swim, tail suspension and open space swim tests were used to collect data on depression-related symptoms. We used the open field test to assess locomotor activity. After the first phase of experiments, dose response curves were plotted and the median dose (ED50) of drugs were calculated using non-linear regression analysis of the dose response curves. From this analysis, the sub-therapeutic dose of iron was selected. In phase 2, the effect of sub-therapeutic dose of iron plus imipramine or citalopram on depression was evaluated using the murine models stated previously. After these behavioral tests, the ELISA test was used to assess concentration of brain-derived neurotrophic factor levels while the Golgi-Cox technique provided information on dendritic spine density of treatment mice.

在本研究中，我们提出假设，铁的低剂量治疗水平与诸如西酞普兰和丙咪嗪等经典抗抑郁药联合使用，将在小鼠中产生快速起效的抗抑郁样效应。首先，研究评估了铁、西酞普兰或丙咪嗪单独在啮齿动物行为模型中的抗抑郁作用。通过强迫游泳、尾部悬挂和开放式游泳测试等行为测试，收集了与抑郁相关症状的数据。利用开放场测试评估运动活动。在实验的第一阶段结束后，绘制剂量反应曲线，并利用非线性回归分析剂量反应曲线来计算药物的半数有效剂量（ED50）。通过此分析，选定了铁的低剂量治疗水平。在第二阶段，通过之前所述的啮齿动物模型，评估了铁的低剂量治疗水平与丙咪嗪或西酞普兰联合使用对抑郁的影响。在行为测试之后，使用ELISA测试评估脑源性神经营养因子水平，而高尔基-考克斯技术则提供了关于治疗小鼠树突棘密度的信息。