Juvenile rats in the forced-swim test model the human response to antidepressant treatment for pediatric depression

Abstract

Rationale: Currently, there are limited treatment options for major depressive disorder in children and adolescents compared to the options available for adults. Many effective treatments used for adult depression, such as the tricyclic antidepressants, lack efficacy when given to children and adolescents.

Objective: To more quickly identify compounds that could be effective for treating childhood and adolescent depression, a reliable preclinical animal behavioral test of antidepressant efficacy for pediatric depression is needed. The forced-swim test (FST) with juvenile rats was assessed to determine its reliability as a predictive model for pediatric depression.

Materials and methods: We adapted procedures from the adult FST to test 21-day-old juvenile rats. The 21-day-old animals were treated with three classes of antidepressant drugs before being assessed in the FST: the selective serotonin reuptake inhibitors escitalopram or fluoxetine; the tricyclic antidepressants desipramine or imipramine; and the monoamine oxidase inhibitor tranylcypromine.

Results: The 21-day-old rats showed dose-dependent changes in behaviors similar to those seen in adults when treated with escitalopram or fluoxetine. Tranylcypromine also decreased immobility in 21-day-old rats. Treatment with desipramine or imipramine, however, was not effective at reducing immobility in the 21-day-old rats.

Conclusions: The juvenile FST accurately predicts the efficacy of selective serotonin reuptake inhibitors and the lack of efficacy of tricyclic antidepressants in the treatment of depression in children and adolescents. This suggests that the FST using 21-day-old rats may help to develop better treatments for childhood and adolescent depression.