title: Agmatine enhances antidepressant potency of MK-801 and conventional antidepressants in mice.
abstract: 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 (0.0001 mg/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.
authors.affiliation: Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário, Trindade 88040-900, Florianópolis, SC, Brazil; Neuroscience Graduate Program, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Vivian Binder
authors.initials: VB
authors.lastname: Neis
authors.affiliation: Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário, Trindade 88040-900, Florianópolis, SC, Brazil; Neuroscience Graduate Program, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil; Department of Natural Sciences, Universidade Regional de Blumenau, Blumenau 89012-900, SC, Brazil.
authors.forename: Morgana
authors.initials: M
authors.lastname: Moretti
authors.affiliation: Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário, Trindade 88040-900, Florianópolis, SC, Brazil; Neuroscience Graduate Program, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Luana Meller
authors.initials: LM
authors.lastname: Manosso
authors.affiliation: Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário, Trindade 88040-900, Florianópolis, SC, Brazil; Neuroscience Graduate Program, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Lopes
authors.affiliation: Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário, Trindade 88040-900, Florianópolis, SC, Brazil; Neuroscience Graduate Program, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil; Biochemistry Graduate Program, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Rodrigo Bainy
authors.initials: RB
authors.lastname: Leal
authors.affiliation: Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário, Trindade 88040-900, Florianópolis, SC, Brazil; Neuroscience Graduate Program, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil; Biochemistry Graduate Program, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. Electronic address: alsrodri@gmail.com.
authors.forename: Ana Lúcia S
authors.initials: AL
authors.lastname: Rodrigues
mesh_terms: D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D016642:Bupropion / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D019417:Hindlimb Suspension; D007099:Imipramine / Q000494:pharmacology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects
chemical_list: D000928:Antidepressive Agents; D005473:Fluoxetine; D016642:Bupropion; D016291:Dizocilpine Maleate; D000376:Agmatine; D007099:Imipramine
keywords: Agmatine; Antidepressants; Depression; NMDA