Original Article

Exp Neurobiol 2015; 24(2): 156-168

Published online June 30, 2015

© The Korean Society for Brain and Neural Sciences

Chronic Antidepressant Treatment in Normal Mice Induces Anxiety and Impairs Stress-coping Ability

In-Sun Baek1,2#, Jin-Young Park1# and Pyung-Lim Han1,2*

Departments of 1Brain and Cognitive Sciences and 2Chemistry and Nano Science, Ewha Womans University, Seoul 120-750, Korea

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-2-3277-4130, FAX: 82-2-3277-3419
#These authors contributed equally to this work.

Received: May 19, 2015; Revised: May 29, 2015; Accepted: May 30, 2015


Antidepressants are clinically used for patients with major depression. Antidepressant treatments in certain groups of patients are effective for relieving depression as well as anxiety disorder. However, it is not clearly known whether the use of current antidepressants in healthy persons is beneficial for upcoming depression- and anxiety-inducing life events. To address this question, normal mice were intraperitoneally administered with imipramine or fluoxetine for more than 2 weeks, and behaviors related to anxiety and depression were evaluated. Mice treated with imipramine or fluoxetine for more than 14 days exhibited significantly decreased immobility time in the forced swim test and tail suspension test, but these mice exhibited enhanced anxiety in several behavioral tests. Furthermore, chronic antidepressant treatments followed by sub-threshold level of stress in normal mice profoundly aggravated antidepressant-induced anxiety-like behaviors without further affecting depression-related behaviors. Chronic antidepressant treatments followed by sub-threshold level of stress produced swollen vesicles and ulcerations on the lips as well as a watery and inflammatory nose. Mice given chronic antidepressant treatments displayed intestinal abnormalities evidenced by a highly enlarged and inflamed small intestine full of defecation materials. These results suggest that chronic antidepressant treatment in normal mice provokes anxiety-like behaviors and impairs their stress-coping ability.

Keywords: Antidepressant, side effects, anxiety, stress-coping response