The behavioral and neurochemical aspects of the interaction between antidepressants and unpredictable chronic mild stress

Abstract

The behavioral and neurochemical effects of amitriptyline (10 mg/kg, i.p.) and fluoxetine (20 mg/kg, i.p.) after single and chronic administration in the setting of unpredictable mild stress in outbred mice ICR (CD-1) were studied. After 28-day exposure to stress we observed an increase in depressive reactions in forced swim test in mice and decrease in serotonin (5-HT) and 5-oxyindol acetic acid (5-HIAA) levels in hippocampus, an increase in noradrenaline (NA) concentration in hypothalamus. Single and chronic administration of amitriptyline and fluoxetine led to shortening of immobilization and increase in swimming in forced swim test. The antidepressant-like effect of fluoxetine, but not of amitriptyline, after single injection coincided with an increase of 5-HT turnover in hippocampus. The chronic administration of the antidepressants caused an increase in NA levels in hypothalamus. Thus, antidepressant-like effect of amitriptyline and fluoxetine may arise from enhancement of stress-dependent adaptive mechanisms depleted by chronic stress.