Combination of resveratrol and fluoxetine in an acute model of depression in mice: Prevention of oxidative DNA fragmentation and monoamines degradation

Resveratrol (RSV) is a natural polyphenol with diverse biological activities, including potent hepato-protective and antidepressant-like effects. Fluoxetine (FLX) is one of the most commonly prescribed antidepressant drugs, however; it has recently been postulated to induce liver damage. The present study aimed to assess the benefits of combining half the conventional doses of RSV and FLX in an acute reserpine model of depression. Depression was induced in mice by a single i.p. reserpine injection. Oral administration of FLX (10 mg/kg), RSV (80 mg/kg) or their combination (FLX; 5 mg/kg and RSV; 40mg/kg) started one hour after reserpine injection and daily for the following two consecutive days. Behavioral tests were performed on the third day. Brain monoamines were assessed. Prevention of neurodegeneration and preservation potential of the DNA integrity were determined according to the brain nitric oxide and 8-hydroxy-2-deoxyguanosine contents. Effect on oxidative stress in both brain and liver was evaluated. Results revealed that combining half the dose of FLX with RSV showed antidepressant activity that was comparable to the effect of using FLX alone and in conclusion; we recommend that further investigations should be conducted to assess the applicability of using combinations of RSV and FLX to treat depression.