A re-evaluation of social defeat as an animal model of depression.

Social defeat by aggressive Tryon Maze Dull (TMD) rats, resulting in loss of rank of a previously dominant rat, has recently been advanced as a model of loss of self-esteem in humans. Since low self-esteem is a major symptom of depression, a further claim has been made that loss of rank can be used as a model of depression. In support of this claim, it has been suggested that loss of rank can be reversed by the antidepressant imipramine. However, antidepressant treatment has not yet been shown to reverse the effects of defeat for more than a single test session. Consequently, the present study was designed to more fully assess the effects of antidepressant treatment on the behaviour of defeated animals. Six pairs of male Lister Hooded (LH) rats were observed biweekly for 30 min at the onset of the dark phase of the light-dark cycle. In five of the six pairs, a stable social hierarchy (assessed by the observation of aggressive behaviours such as attacks and pushes, and submissive behaviours such as submissive posture) was established over a period of 10 weeks. The dominant animals of these five pairs were defeated once a week, in the home cage, by a singly housed male TMD for a period of 15 min. After 5 weeks of defeat by TMD, all five of the dominant animals showed an effect of defeat on behaviours relevant to status, although a reversal in status within the LH pairs was apparent in only one case. All defeated animals, regardless of whether or not defeat affected status, received daily injections of imipramine (5 mg/kg) for 5 weeks. Imipramine markedly worsened behaviours relevant to status in the treated animals. Indeed, animals treated with imipramine were more likely to lose encounters with their cage-mates. Consequently, the results cast doubt on the validity of social defeat as a model of depression, at least when the effects of defeat are assessed in terms of social status.