Abstract
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.
Highlights
Depression is one of the most common neuropsychiatric disorders that affect approximately 20% of the world population (Schechter, 2005; Thakare and Patel, 2015)
These reports led us to investigate the effect of combining the well-known hepato-protective and potential antidepressant RSV with FLX to alleviate the depressive-like behaviors in mice induced by single intraperitoneal (i.p.) reserpine injection and whether this combination would result in antidepressant effect that is comparable to that of the conventional dose of FLX
Results of the present study revealed that acute reserpine injection resulted in depressive-like behaviors such as decrease in the mice activity in the activity cage, increased immobility durations in both the TST and FST along with other physiological changes represented by prolonged monoamines depletion and oxidative stress
Summary
Depression is one of the most common neuropsychiatric disorders that affect approximately 20% of the world population (Schechter, 2005; Thakare and Patel, 2015) It can be caused by one or more changes in the brain, which may or may not be directly related. It has been reported that FLX therapy could be associated with hepatic side effects due to its fluorine content (Beasley et al, 2000; Inkielewicz-Stepniak, 2011) These reports led us to investigate the effect of combining the well-known hepato-protective and potential antidepressant RSV with FLX to alleviate the depressive-like behaviors in mice induced by single intraperitoneal (i.p.) reserpine injection and whether this combination would result in antidepressant effect that is comparable to that of the conventional dose of FLX. In order to achieve our aim, the behavioral, biochemical and neurochemical changes were assessed
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