PDF(Pubmed)
Abstract：
The etiology of major depressive disorder (MDD) remains poorly understood. Our previous studies suggest a role for the aryl hydrocarbon receptor (AhR) in depression. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a toxic environmental contaminant, with a high AhR binding affinity, and an established benchmark for assessing AhR activity. Therefore, this study examined the effect of TCDD on depression-like behaviors. Female mice were fed standard chow or a high-fat diet (HFD) for 11 weeks, and their weight was recorded. Subsequently, they were tested for baseline sucrose preference and splash test grooming. Then, TCDD (0.1 µg/kg/day) or vehicle was administered orally for 28 days, and mice were examined for their sucrose preference and performances in the splash test, forced swim test (FST), and Morris water maze (MWM) task. TCDD significantly decreased sucrose preference, increased FST immobility time, and decreased groom time in chow-fed mice. HFD itself significantly reduced sucrose preference. However, TCDD significantly increased FST immobility time and decreased groom time in HFD-fed mice. A small decrease in bodyweight was observed only at the fourth week of daily TCDD administration in chow-fed mice, and no significant effects of TCDD on bodyweights were observed in HFD-fed mice. TCDD did not have a significant effect on spatial learning in the MWM. Thus, this study demonstrated that TCDD induces a depression-like state, and the effects were not due to gross lethal toxicity. This study further suggests that more studies should examine a possible role for AhR and AhR-active environmental pollutants in precipitating or worsening MDD.
摘要：
重度抑郁症（MDD）的病因仍然知之甚少。我们先前的研究表明，芳香烃受体（AhR）在抑郁症中的作用。2,3,7,8-四氯二苯并对二恶英（TCDD）是一种有毒的环境污染物，具有高AhR结合亲和力，以及评估AhR活动的既定基准。因此,本研究探讨了TCDD对抑郁样行为的影响。雌性小鼠饲喂标准食物或高脂肪饮食（HFD）11周，记录了他们的体重。随后，他们进行了基线蔗糖偏好和飞溅测试梳理测试。然后，口服TCDD（0.1µg/kg/天）或赋形剂28天，并在飞溅试验中检查小鼠的蔗糖偏好和表现，强迫游泳测试（FST）和莫里斯水迷宫（MWM）任务。TCDD显著降低蔗糖偏好，增加FST不动时间，并减少了喂食小鼠的新郎时间。HFD本身显著降低蔗糖偏好。然而,在HFD喂养的小鼠中,TCDD显著增加FST不活动时间和减少新郎时间。仅在每天喂食TCDD的小鼠的第四周观察到体重的小幅下降，在HFD喂养的小鼠中没有观察到TCDD对体重的显著影响。TCDD对MWM中的空间学习没有显着影响。因此，这项研究表明，TCDD诱导抑郁样状态，和影响不是由于总致死毒性。这项研究进一步表明，更多的研究应该研究AhR和AhR活性环境污染物在沉淀或恶化MDD中的可能作用。
