RESEARCH ARTICLE Dissociation of Learned Helplessness and Fear Conditioning in Mice: A Mouse Model of Depression

The state of being helpless is regarded as a central aspect of depression, and therefore the learned helplessness paradigm in rodents is commonly used as an animal model of depres-sion. The term ‘learned helplessness ’ refers to a deficit in escaping from an aversive situa-tion after an animal is exposed to uncontrollable stress specifically, with a control/ comparison group having been exposed to an equivalent amount of controllable stress. A key feature of learned helplessness is the transferability of helplessness to different situa-tions, a phenomenon called ‘trans-situationality’. However, most studies in mice use learned helplessness protocols in which training and testing occur in the same environment and with the same type of stressor. Consequently, failures to escape may reflect condi-tioned fear of a particular environment, not a general change of the helpless state of an ani-mal. For mice, there is no established learned helplessness protocol that includes the trans-situationality feature. Here we describe a simple and reliable learned helplessness protocol for mice, in which training and testing are carried out in different environments and with dif-ferent types of stressors. We show that with our protocol approximately 50 % of mice devel-op learned helplessness that is not attributable to fear conditioning