A missing link between depression models: Forced swimming test, helplessness and passive coping in genetically heterogeneous NIH-HS rats.

The forced swimming test (FST) and helplessness reactions at two-way active escape/avoidance task are used in the study of depressive-like symptoms and antidepressant treatments in rodents. In both tests/tasks the animals are submitted to stressful situations, known to induce several responses that have been considered as parallels of some symptoms of the human depressive disorder. However, there is a lack of experimental evidence supporting associations between the behavioral responses displayed in both behavioral procedures by outbred rats. The objective of the present study was to evaluate the possible associations between the behavioral responses in both depression models using the National Institutes of Health genetically heterogeneous rat stock (i.e. NIH-HS rats). To this aim, 97 NIH-HS rats were submitted to both behavioral procedures (FST and two-way active escape task under a fixed ratio 2 - FR2). The statistical analyses comparing the sub-groups of rats selected by their high or low behavioral responses in either the FST or the FR2 helplessness task showed associations between the responses evaluated in both tests. Specifically, higher levels of struggling (i.e. vigorous swimming directed to escape from the FST) or less time of immobility in the first session of FST predicted lesser response failures in the FR2 two-way active escape (helplessness) task. In parallel, the stratification of rats for their high or low scores of response failures in the FR2 task was predictive of their levels of struggling in the FST. Thus, it is demonstrated for the first time that passive coping responses in one test are predictive of similar coping styles in the other task. The present findings may be relevant for the concurrent validity of both depression models.