Agmatine enhances antidepressant potency of MK-801 and conventional antidepressants in mice

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 2015-03, Vol.130, p.9-14
• Main Authors: Neis, Vivian Binder, Moretti, Morgana, Manosso, Luana Meller, Lopes, Mark W., Leal, Rodrigo Bainy, Rodrigues, Ana Lúcia S.
• Format: Article
• Language: English
• Subjects: Agmatine; Agmatine - pharmacology; Animals; Antidepressants; Antidepressive Agents - pharmacology; Bupropion - pharmacology; Depression; Dizocilpine Maleate - pharmacology; Dose-Response Relationship, Drug; Drug Synergism; Female; Fluoxetine - pharmacology; Hindlimb Suspension; Imipramine - pharmacology; Mice; Motor Activity - drug effects; NMDA
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2014.12.009

Agmatine, an endogenous guanidine amine, has been shown to produce antidepressant-like effects in animal studies. This study investigated the effects of the combined administration of agmatine with either conventional monoaminergic antidepressants or the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 in the tail suspension test (TST) in mice. The aim was to evaluate the extent of the antidepressant synergism by examining the ability of a fixed dose of agmatine to shift the antidepressant potency of fluoxetine, imipramine, bupropion and MK-801. A sub-effective dose of agmatine (0.0001mg/kg, p.o.) significantly increased the potency by which fluoxetine, imipramine, bupropion and MK-801 decreased immobility time in the TST by 2-fold (fluoxetine), 10-fold (imipramine and bupropion) and 100-fold (MK-801). Combined with previous evidence indicating a role of monoaminergic systems in the effect of agmatine, the current data suggest that agmatine may modulate monoaminergic neurotransmission and augment the activity of conventional antidepressants. Moreover, this study found that agmatine substantially augmented the antidepressant-like effect of MK-801, reinforcing the notion that this compound modulates NMDA receptor activation. These preclinical data may stimulate future clinical studies testing the effects of augmentation therapy with agmatine for the management of depressive disorders. •Agmatine caused a 2-fold increase in the potency of fluoxetine in the TST.•Agmatine caused a 10-fold increase in the potency of imipramine and bupropion.•The antidepressant potency of MK-801 was increased by 100-fold by agmatine.•Agmatine may modulate monoaminergic systems and NMDA receptors.