Major depressive disorder not only affects adults but is also commonly diagnosed in children and adolescents. Once diagnosed, children and adolescents are then treated with drugs that were developed for the adult population. This is problematic as research suggests that children and adolescents respond differently to antidepressants than adults. Antidepressants for adult depression were first tested for antidepressant activity by utilizing behavioral models of depression with adult animals. There are no documented behavioral models of depression specifically designed to study childhood and adolescent depression. The purpose of the following experiments was to develop a reliable behavioral model of juvenile depression that can then be used to test antidepressant efficacy in juvenile animals.

We tested 21-day old male Sprague-Dawley rats in three behavioral tests used regularly to study antidepressant properties of compounds: the tail-suspension test (TST), the forced-swim test (FST), and a learned helplessness (LH) paradigm. All are behavioral models of depression used for screening antidepressant efficacy. In both the FST and LH models, 21-day rats treated with selective serotonin reuptake inhibitors (SSRIs) showed a prevention of behavioral despair, similar to results obtained with adults. When 21-day rats were treated with tricyclic antidepressants (TCAs), there was no prevention of behavioral despair similar to controls. This is in contrast to adult studies which show TCA treatment is 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 to the response of children and adolescents to antidepressant treatment, as they respond to SSRIs but not TCAs. Several other compounds effective at decreasing immobility in the adult FST were then screened for effectiveness using the juvenile FST. Screening these drugs for antidepressant effects in the juvenile FST helped to narrow the focus of further efforts to develop compounds that would be useful for treating childhood and adolescent depression. Further studies using both the FST and LH models in 21-day animals may eventually help to better understand and treat pediatric depression.