摘要
Objective Striatum may be involved in depressive disorders according to the neuroimaging analysis and clinical data. However, no animal model at present supported the possible role of striatum in the pathogenesis of depression. In the present study, we have investigated the depressive-like behavior in mice recently intoxicated with 3-nitropropionic acid （3- NP）, a widely known toxin that selectively damages the striatum in the brain. Methods Mouse model was made with subacute systemic 3-NP treatment, and the depressive-like behavior was measured using the duration of immobility during forced swimming test （FST）. Results When the mice at day 15 post-intoxication just totally recovered from motor deficits, the duration of immobility in FST was significantly longer than that in controls. The depressive-like behavior was not due to the fatigue or general sickness following 3-NP intoxication and could be reversed by the antidepressant, desipramine hydrochloride. In two successive FST in 24 h interval, the depressive-like behavior could be observed again in subsequent FST （at day 16 post-intoxication）, and the mice presented a normal ＂learned helplessness＂. Conclusion A novel depression animal model could be established in mice during the initial period of recovery from 3-NP intoxication. The depression-like behavior might occur independently without involvement of cognitive defects, and the striatal lesions may underlie the depression-like behavior attributable to 3-NP intoxication.
目的纹状体可能与抑郁症的发生有关,但是目前还没有动物实验模型支持纹状体在抑郁症发病过程中的可能作用的证据。本研究在选择性损伤纹状体的3-硝基丙酸(3-NP)中毒动物实验模型上,观察小鼠是否出现抑郁样症状。方法采用亚急性系统给予3-NP的方式制作小鼠实验模型,用强迫游泳实验(forced swimming test, FST)中的漂浮时间评价小鼠的抑郁样症状。结果在注射3-NP后的15天,即小鼠完全恢复运动功能后的早期,小鼠在FST中的漂浮时间较对照组明显延长。这种抑郁样症状不是由于3-NP中毒后引起的疲劳或虚弱所造成,可被抗抑郁药去甲丙米嗪消除。在间隔24 h的两次FST中,可在24 h后(3-NP中毒后16天)FST中再次观察到这种抑郁样症状,小鼠还显示如常的习得性无助反应。结论在3-NP中毒恢复期小鼠可建立一种新型的动物抑郁模型,小鼠的抑郁样症状可能不涉及认知缺陷而独立存在,而纹状体的损伤可能与3-NP中毒后抑郁样症状的产生有关。
