Effects of Unpredictable Chronic Mild Stress on the Effects of Antidepressants in the Forced Swimming Test

Abstract

The effects of unpredictable chronic mild stress on the effects of the tricyclic antidepressant amitriptyline (10 mg/kg) and the selective serotonin reuptake inhibitor fluoxetine (20 mg/kg) in the Porsolt test were studied in male mongrel mice. Single doses of fluoxetine given after 14-day chronic mild stress lacked any antidepressant effect, while subchronic administration for 14 days strengthened depressive-like reactions. After stress for 28 days, the antidepressant effect of fluoxetine was present regardless of the number of doses given. Amitriptyline showed antidepressant activity independently of the duration of stress and the administration regime, though the presence of stress decreased the intensity of the antiimmobility effect. Thus, the number of doses and the duration of unpredictable mild stress are parameters determining the efficacy of antidepressants in the forced swimming test.