MOE Key Laboratory of Modern Teaching Technology, Center for Teacher Professional Ability Development, Shaanxi Normal University, Xi'an, 710062, China.
College of Life Sciences, Shaanxi Normal University, Xi'an, 710062, China.
Behav Brain Res. 2019 Dec 30;376:112173. doi: 10.1016/j.bbr.2019.112173. Epub 2019 Aug 22.
Most of the pathophysiology of depression are still unknown because of its numerous disease states of distinct etiology and pathogenesis. Stressful rodent models have been used to test a number of hypotheses regarding the etiology of depression. The learned helplessness rodent model demonstrates that having no control at all over aversive events produces helplessness and depression, but the role of loss of control over aversive events in helplessness is still not reliably modelled or deeply investigated. A rodent model of helplessness produced by loss of control is closer to human conditions and is therefore more useful for novel mechanistic and pre-clinic studies. The present work proposed a triadic experimental design in which a Loss Of Control (LOC) group of mice was firstly exposed to escapable mild footshocks to acquire control, and then to inescapable shocks to lose control, with a yoked (L-Yoked) group receiving identical but always uncontrollable shocks. Although both the LOC and the L-Yoked groups developed helplessness, as compared with the naive control group, the helplessness exhibited in the LOC group was significantly more serious than that in the L-Yoked group. The difference in severity between the LOC and the L-Yoked groups demonstrates the effects of loss of control over aversive events, in addition to the effects of the aversive events per se. The LOC paradigm can be used to reproduce pathology of depression induced by loss of control over aversive life events, with a good constructive validity.
由于抑郁症有许多不同病因和发病机制的疾病状态，其病理生理学的大部分仍不清楚。应激啮齿动物模型被用于测试许多关于抑郁症病因的假设。习得性无助啮齿动物模型表明，对令人痛苦的事件完全没有控制会导致无助和抑郁，但对令人痛苦的事件失去控制在无助中的作用仍未得到可靠的模拟或深入研究。对失去控制导致的无助的啮齿动物模型更接近人类的情况，因此更有助于进行新的机制和临床前研究。本研究提出了一个三重实验设计，其中一组小鼠首先暴露于可逃避的轻度足部电击中以获得控制，然后暴露于不可逃避的电击中以失去控制，一组配对（L-Yoked）组接受相同但始终无法控制的电击。尽管 LOC 组和 L-Yoked 组都表现出了无助，但与未处理的对照组相比，LOC 组的无助表现明显更为严重。LOC 组和 L-Yoked 组之间严重程度的差异表明，除了令人痛苦的事件本身的影响外，对令人痛苦的事件失去控制也会产生影响。LOC 范式可用于再现由对令人痛苦的生活事件失去控制引起的抑郁病理学，具有良好的构建效度。
