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

作者：Neis Vivian B; Bettio Luis E B; Moretti Morgana; Rosa Priscila B; Ribeiro Camille M; Freitas Andiara E; Goncalves FiliPe M; Leal Rodrigo B; Rodrigues Ana Lucia S^*

来源：Pharmacology Biochemistry and Behavior, 2016, 150: 108-114.

DOI：10.1016/j.pbb.2016.10.004

• Agmatine
• Chronic unpredictable stress(CUS)
• Fluoxetine
• Ketamine
• Synaptic proteins

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 14 days, mice received a single oral dose of agmatine (0.1 mg/kg), ketamine (1 mg/kg) or fluoxetine (10 mg/kg), and were submitted to behavioral evaluation after 24 h. 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.

• 出版日期2016-12