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


CONCLUSIONS
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.
West
Charles Hutchison Keesor
CH
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
Weiss
Jay Michael
JM
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004597:Electroshock; D004924:Escape Reaction / Q000187:drug effects*; D005239:Fear / Q000187:drug effects*; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000150:complications*; D013550:Swimming
D000928:Antidepressive Agents