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A selective test for antidepressant treatments using rats bred for stress-induced reduction of motor activity in the swim test

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Abstract

Rationale and objective

This paper describes a new procedure for detecting effective antidepressant treatments. The procedure uses the swim-test susceptible (Susceptible) rat which has been selectively bred to show decreased struggling behavior in a swim test after exposure to a mild stressor. The ability of treatments to block this decrease in swim-test activity was assessed as a method for detecting effective antidepressants.

Results

In both male and female Susceptible rats, chronic (14-day) treatment with different antidepressant drugs delivered via osmotic minipump [i.e., three tricyclics (desmethylimipramine, imipramine, amitriptyline), two selective serotonin reuptake inhibitors (fluoxetine and sertraline), a monoamine oxidase inhibitor (phenelzine), and two atypical antidepressants (venlafaxine and bupropion)] all prevented the stress-induced decrease in swim-test struggling normally shown by these rats. Electroconvulsive shock had a similar effect. Unlike antidepressant drugs, 14-day treatment with various nonantidepressant drugs [i.e., a stimulant (amphetamine), an anxiolytic (chlordiazepoxide), an antihistamine (chlorpheniramine), and an anticholinergic (scopolamine)] did not have this effect. Antidepressant drug treatment for 1 day (i.e., acute treatment) was also ineffective in this test. The procedure described above requires use of the Susceptible rat—swim test resistant rats (i.e., rats selectively bred to be resistant to decreased swim-test activity after exposure to stressful conditions) showed no significant differences in swim-test behavior between stress and nonstress conditions after 14-day drug treatment, and randomly bred Sprague–Dawley rats did not show a decrease in swim-test activity following exposure to the mild stressor that is the basis for the test.

Conclusion

These results suggest that the procedure described here, which uses a rat subject that has been bred for vulnerability to stressful conditions, may be a selective screening technique for effective antidepressant treatments.

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Acknowledgements

This research was supported by the Theodore and Vada Stanley Foundation of the National Alliance for the Mentally Ill (NAMI). We acknowledge with appreciation the following pharmaceutical companies for generously providing the indicated drugs: Eli Lilly, Indianapolis, IN (fluoxetine), Wyeth-Ayerst, Princeton, NJ (venlafaxine), Burroughs Wellcome, Research Triangle Park, NC (bupropion), and Pfizer, Groton, CN, (sertraline). The authors gratefully acknowledge the excellent technical assistance of Sandra Parks and Lorna Clarke in the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, 30322, USA

    Charles Hutchison Keesor West & Jay Michael Weiss

  2. Emory West Campus, Building A, Room 510-N, 1256 Briarcliff Road, N.E., Atlanta, GA, 30306, USA

    Jay Michael Weiss

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  1. Charles Hutchison Keesor West
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Correspondence to Jay Michael Weiss.

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West, C.H.K., Weiss, J.M. A selective test for antidepressant treatments using rats bred for stress-induced reduction of motor activity in the swim test. Psychopharmacology 182, 9–23 (2005). https://doi.org/10.1007/s00213-005-0048-x

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  • DOI: https://doi.org/10.1007/s00213-005-0048-x

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