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

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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.

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Acknowledgments

This research was supported by a grant from the Mental Health Institute of the National Institutes of Health number MH66959 and a Creighton University Health Future Foundation internal grant. ALR was also in part supported by a fellowship from the Nebraska IDeA Networks of Biomedical Research Excellence (NE-INBRE), grant number P20 RR16469. The authors would like to thank Jeffrey Anderson for his technical assistance in helping with the adult FST. All experiments comply with the current laws of the country in which they were performed.

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Authors and Affiliations

  1. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985800 Nebraska Medical Center, Omaha, NE, 68198, USA

    Abbey L. Reed & David B. Bylund

  2. Department of Psychiatry, Creighton University, 3528 Dodge Street, Omaha, NE, 68131, USA

    H. Kevin Happe & Frederick Petty

  3. Omaha Veterans Administration Medical Center, 4101 Woolworth Avenue, Omaha, NE, 68105, USA

    H. Kevin Happe & Frederick Petty

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  1. Abbey L. Reed
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  2. H. Kevin Happe
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  3. Frederick Petty
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  4. David B. Bylund
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Correspondence to Abbey L. Reed.

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Reed, A.L., Happe, H.K., Petty, F. et al. Juvenile rats in the forced-swim test model the human response to antidepressant treatment for pediatric depression. Psychopharmacology 197, 433–441 (2008). https://doi.org/10.1007/s00213-007-1052-0

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  • DOI: https://doi.org/10.1007/s00213-007-1052-0

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