Title:Study of the Antidepressant Effects of the Combination of Agmatine and
Melatonin Following Restraint Stress in Mice: the Role of Oxidative
Factors
Volume: 26
Issue: 1
Author(s): Saeed Mehrzadi, Ali Jamshidi Naeini, Fahime Azimirad and Azam Hosseinzadeh*
Affiliation:
- Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran
Keywords:
Pharmacology, oxidative stress, melatonin, depression, agmatine, hippocampus catalase activity, hippocampus antioxidant activity.
Abstract:
Objective: Major Depressive Disorder (MDD) is a psychiatric disorder that has a tight
connection to stressful experiences, decreased levels of endogenous antioxidants and enhanced levels
of oxidative stress. We drafted this research to define the results of combining agmatine and
melatonin on stress-induced depression in mice.
Methods: Experimental groups included the non-stressed group treated with vehicle (ethanol at a
concentration of 0.0005%), stressed vehicle (ethanol at a concentration of 0.0005%)-treated group,
group treated with fluoxetine (10 mg/kg/day), group treated with melatonin (10 mg/kg/day), group
treated with agmatine (1 mg/kg/day), group receiving a combination of melatonin (10 mg/kg/day)
and agmatine (1 mg/kg/day). The animals were subjected to restraint stress for two hours daily for
a duration of one week, concurrently with the daily oral administration of agents through drinking
water. Open field test and forced swimming test were operated on the 8th day. The oxidative stress
markers were measured in the mice hippocampus.
Results: Stress led to the elevation of immobility time. The combination group showed a significant
effect in comparison to the agmatine and melatonin groups. The combination of melatonin and
agmatine was successful in the elevation of hippocampus catalase activity; and this effect was
comparable in the fluoxetine group. We observed enhancement of superoxide dismutase activity in
treatment groups and reduction in malondialdehyde levels in melatonin, agmatine and combination
groups.
Conclusion: A combination of agmatine and melatonin improves stress-induced depression more
effectively than each alone, which may result from suppressing oxidative stress.
