Acute agmatine administration, similar to ketamine, reverses depressive-like behavior induced by chronic unpredictable stress in mice

Agmatine is an endogenous neuromodulator that has been shown to have antidepressant-like properties. We have previously demonstrated that it can induce a rapid increase in BDNF levels after acute administration, suggesting that agmatine may be a fast-acting antidepressant. To investigate this hypoth...

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Published in:Pharmacology, biochemistry and behavior biochemistry and behavior, 2016-11, Vol.150-151, p.108-114
Main Authors: Neis, Vivian B, Bettio, Luis E B, Moretti, Morgana, Rosa, Priscila B, Ribeiro, Camille M, Freitas, Andiara E, Gonçalves, Filipe M, Leal, Rodrigo B, Rodrigues, Ana Lúcia S
Format: Article
Language:English
Subjects:
Agmatine - pharmacology
Animals
Antidepressive Agents - pharmacology
Depressive Disorder - drug therapy
Female
Hindlimb Suspension
Ketamine - pharmacology
Mice
Motor Activity - drug effects
Prefrontal Cortex - chemistry
Stress, Psychological - complications
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Summary:Agmatine is an endogenous neuromodulator that has been shown to have antidepressant-like properties. We have previously demonstrated that it can induce a rapid increase in BDNF levels after acute administration, suggesting that agmatine may be a fast-acting antidepressant. To investigate this hypothesis, the present study evaluated the effects of a single administration of agmatine in mice subjected to chronic unpredictable stress (CUS), a model of depression responsive only to chronic treatment with conventional antidepressants. The ability of agmatine to reverse CUS-induced behavioral and biochemical alterations was evaluated and compared with those elicited by the fast-acting antidepressant (ketamine) and the conventional antidepressant (fluoxetine). After exposed to CUS for 14days, mice received a single oral dose of agmatine (0.1mg/kg), ketamine (1mg/kg) or fluoxetine (10mg/kg), and were submitted to behavioral evaluation after 24h. The exposure to CUS caused an increased immobility time in the tail suspension test (TST) but did not change anhedonic-related parameters in the splash test. Our findings provided evidence that, similarly to ketamine, agmatine is able to reverse CUS-induced depressive-like behavior in the TST. Western blot analyses of prefrontal cortex (PFC) demonstrated that mice exposed to CUS and/or treated with agmatine, fluoxetine or ketamine did not present alterations in the immunocontent of synaptic proteins [i.e. GluA1, postsynaptic density protein 95 (PSD-95) and synapsin]. Altogether, our findings indicate that a single administration of agmatine is able to reverse behavioral alterations induced by CUS in the TST, suggesting that this compound may have fast-acting antidepressant-like properties. However, there was no alteration in the levels of synaptic proteins in the PFC, a result that need to be further investigated in other time points.
ISSN:0091-3057
1873-5177
DOI:10.1016/j.pbb.2016.10.004