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.本研究提出假说：亚治疗剂量的铁剂与西酞普兰、丙咪嗪等经典抗抑郁药物联合使用时，可在小鼠模型中产生快速起效的抗抑郁样作用。首先，本研究在小鼠行为学模型中单独评估了铁剂、西酞普兰或丙咪嗪的抗抑郁效应。采用强迫游泳实验、悬尾实验及开阔水域游泳实验等行为学检测手段，采集与抑郁样症状相关的数据；同时通过旷场实验评估小鼠的运动活性。第一阶段实验结束后，我们绘制了各药物的量效曲线，并通过量效曲线的非线性回归分析计算得到各药物的半数有效剂量（ED50），据此筛选出铁剂的亚治疗剂量。第二阶段实验中，我们采用前述小鼠行为学模型，评估了亚治疗剂量铁剂联合丙咪嗪或西酞普兰的抗抑郁效应。完成上述行为学检测后，通过酶联免疫吸附实验（ELISA）检测小鼠脑源性神经营养因子（brain-derived neurotrophic factor）的水平，并利用高尔基-科克斯染色技术分析给药小鼠的树突棘密度。