Comparative Effect of Fluoxetine and Imipramine on Social Defeat Stress Model of Depression in Mice

Abstract

Fluoxetine and imipramine are antidepressant drugs used in the management of depression. This study aimed to evaluate the comparative effect of fluoxetine and imipramine on social defeat stress (SDS)-induced depression in mice. Twenty-eight mice were divided into four groups as follows: 1 - Control (distilled water), 2 - untreated SDS, 3 - SDS + fluoxetine (10 mg/kg), and 4 - SDS + imipramine (10 mg/kg). Fluoxetine and imipramine were administered orally once daily for 14 days. At the end of treatment period, behavioural tests, including tail suspension test (TST), forced swim test (FST), sucrose splash test (SST), and social interaction test (SIT) were conducted, after which the animals were sacrificed, and blood samples were collected for biochemical analysis. Mice brain were harvested for immune-histochemical and histological analysis. Results showed that fluoxetine decreased immobility time significantly (p < 0.05) in the TST and FST compared to imipramine, while in SST, imipramine increased sucrose preference significantly (p < 0.05) compared to fluoxetine. Both drugs boosted antioxidant levels in SDS mice, but fluoxetine had a better effect on catalase than imipramine. Both drugs increased levels of corticosterone and norepinephrine to similar extent in the prefrontal cortex (PFC). Fluoxetine significantly (p < 0.05) increased serotonin levels compared to imipramine. Both drugs significantly increased neuronal density to similar extent in the medial PFC, hippocampus, and adrenal gland of SDS mice compared to the untreated SDS mice. This study has revealed that fluoxetine had a better antidepressant effect than imipramine as shown in the behavioural models.