Loss of control over mild aversive events produces significant helplessness in mice.

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.