The forced‐swim test and learned helplessness paradigm in juvenile rats model the lack of efficacy of tricyclic antidepressants in childhood and adolescent depression

A valid and reliable behavioral model of juvenile depression would be useful to develop specific treatments for childhood and adolescent depression. We tested 21-day old male Sprague-Dawley rats in the forced-swim test (FST) and a learned helplessness (LH) paradigm. Both are behavioral models of depression that can screen for antidepressant efficacy. In both models, 21-day rats treated with selective serotonin reuptake inhibitors (SSRIs) showed a prevention of behavioral despair, similar to results obtained with adult rats. When 21-day rats were treated with tricyclic antidepressants (TCAs), there was no prevention of behavioral despair and their behavior was similar to saline controls. This is in contrast to adult studies which show TCA treatment as effective in decreasing behavioral despair in both the FST and LH. The drug response in juvenile rats for both the FST and LH is similar the response of children and adolescents to antidepressant treatment, as they respond to SSRIs but not TCAs. This may be due to the relatively immature adrenergic nervous system, as compared to the serotonergic system, in young animals. These results suggest that the FST and LH in 21-day animals could be used as behavioral models for childhood and adolescent depression. Support: MH66959(DBB); HFF(HKH).