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 non-antidepressant 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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