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Study of the Antidepressant Effects of the Combination of Agmatine and Melatonin Following Restraint Stress in Mice: the Role of Oxidative Factors.

Central nervous system agents in medicinal chemistry
March 25, 2025
Saeed Mehrzadi et al. (4 authors)
Journal ArticleAnimal Study
Study Details

Study Goal

The researchers aimed to determine whether combining agmatine with melatonin could improve stress-induced depression in mice, focusing on oxidative stress markers in the hippocampus.

Results Summary

The combination of agmatine and melatonin significantly reduced immobility time and oxidative stress markers (e.g., increased catalase and superoxide dismutase activity, reduced malondialdehyde levels) compared to either treatment alone, with effects comparable to fluoxetine. Limitations include the use of an animal model and short-term intervention.

Population

Mice subjected to restraint stress (no further demographic details provided).

Effective Dosage

Agmatine (1 mg/kg/day), melatonin (10 mg/kg/day), and fluoxetine (10 mg/kg/day).

Duration

One week of daily administration.

Interactions

None mentioned.

Extracted Claims (10)
InterventionDirectionEndpointPopulationDosageImpactClaim #
restraint stress
increase
immobility time
mice
-
led to the elevation of
#1
combination of melatonin and agmatine
neutral
-
mice
-
showed a significant effect in comparison to
#2
combination of melatonin and agmatine
increase
hippocampus catalase activity
mice
-
was successful in the elevation of
#3
fluoxetine
neutral
hippocampus catalase activity
mice
-
comparable in
#4
treatment groups
increase
superoxide dismutase activity
mice
-
observed enhancement of
#5
melatonin
decrease
malondialdehyde levels
mice
-
reduction in
#6
agmatine
decrease
malondialdehyde levels
mice
-
reduction in
#7
combination of melatonin and agmatine
decrease
malondialdehyde levels
mice
-
reduction in
#8
combination of agmatine and melatonin
neutral
stress-induced depression
mice
-
improves
#9
combination of agmatine and melatonin
decrease
oxidative stress
-
-
may result from suppressing
#10
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.

Study Links
Quality Scores
SafetyNot Assessed
Efficacy80/10
Quality70/10
Research Impact Scores
APT Score0.05
Weight Score1.80
Normalized Score0.66
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