Agmatine abolishes restraint stress-induced depressive-like behavior and hippocampal antioxidant imbalance in mice

Agmatine has been recently emerged as a novel candidate to assist the conventional pharmacotherapy of depression. The acute restraint stress (ARS) is an unavoidable stress situation that may cause depressive-like behavior in rodents. In this study, we investigated the potential antidepressant-like e...

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Bibliographic Details
Published in:Progress in neuro-psychopharmacology & biological psychiatry 2014-04, Vol.50, p.143-150
Main Authors: Freitas, Andiara E., Bettio, Luis E.B., Neis, Vivian B., Santos, Danúbia B., Ribeiro, Camille M., Rosa, Priscila B., Farina, Marcelo, Rodrigues, Ana Lúcia S.
Format: Article
Language:English
Subjects:
Acute restraint stress
Adult and adolescent clinical studies
Agmatine
Agmatine - pharmacology
Agmatine - therapeutic use
Animals
Antidepressive Agents - pharmacology
Antidepressive Agents - therapeutic use
Antioxidant
Antioxidants - metabolism
Biological and medical sciences
Depression
Depression - drug therapy
Depression - metabolism
Female
Forced swimming test
Hippocampus - drug effects
Hippocampus - metabolism
Immobility Response, Tonic - drug effects
Lipid Peroxidation - drug effects
Medical sciences
Mice
Mood disorders
Motor Activity - drug effects
Neuropharmacology
Pharmacology. Drug treatments
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Restraint, Physical - psychology
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Summary:Agmatine has been recently emerged as a novel candidate to assist the conventional pharmacotherapy of depression. The acute restraint stress (ARS) is an unavoidable stress situation that may cause depressive-like behavior in rodents. In this study, we investigated the potential antidepressant-like effect of agmatine (10mg/kg, administered acutely by oral route) in the forced swimming test (FST) in non-stressed mice, as well as its ability to abolish the depressive-like behavior and hippocampal antioxidant imbalance induced by ARS. Agmatine reduced the immobility time in the mouse FST (1–100mg/kg) in non-stressed mice. ARS caused an increase in the immobility time in the FST, indicative of a depressive-like behavior, as well as hippocampal lipid peroxidation, and an increase in the activity of hippocampal superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities, reduced catalase (CAT) activity and increased SOD/CAT ratio, an index of pro-oxidative conditions. Agmatine was effective to abolish the depressive-like behavior induced by ARS and to prevent the ARS-induced lipid peroxidation and changes in SOD, GR and CAT activities and in SOD/CAT activity ratio. Hippocampal levels of reduced glutathione (GSH) were not altered by any experimental condition. In conclusion, the present study shows that agmatine was able to abrogate the ARS-induced depressive-like behavior and the associated redox hippocampal imbalance observed in stressed restraint mice, suggesting that its antidepressant-like effect may be dependent on its ability to maintain the pro-/anti-oxidative homeostasis in the hippocampus. [Display omitted] •ARS causes a depressive-like behavior and a redox hippocampal imbalance.•ARS induced changes in TBARS, SOD, GPx, GR, CAT and SOD/CAT in the hippocampus.•Agmatine produced a significant antidepressant-like effect in the FST.•Agmatine was effective to prevent the behavioral alterations induced by ARS.•Agmatine abolished the ARS-induced changes in TBARS, SOD, GR, CAT and SOD/CAT.
ISSN:0278-5846
1878-4216
DOI:10.1016/j.pnpbp.2013.12.012