title: Effects of Agmatine on Depressive-Like Behavior Induced by Intracerebroventricular Administration of 1-Methyl-4-phenylpyridinium (MPP(+)).
abstract: Considering that depression is a common non-motor comorbidity of Parkinson's disease and that agmatine is an endogenous neuromodulator that emerges as a potential agent to manage diverse central nervous system disorders, this study investigated the antidepressant-like effect of agmatine in mice intracerebroventricularly (i.c.v.) injected with the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)). Male C57BL6 mice were treated with agmatine (0.0001, 0.1 or 1 mg/kg) and 60 min later the animals received an i.c.v. injection of MPP(+) (1.8 µg/site). Twenty-four hours after MPP(+) administration, immobility time, anhedonic behavior, and locomotor activity were evaluated in the tail suspension test (TST), splash test, and open field test, respectively. Using Western blot analysis, we investigated the putative modulation of MPP(+) and agmatine on striatal and frontal cortex levels of tyrosine hydroxylase (TH) and brain-derived neurotrophic factor (BDNF). MPP(+) increased the immobility time of mice in the TST, as well as induced an anhedonic-like behavior in the splash test, effects which were prevented by pre-treatment with agmatine at the three tested doses. Neither drug, alone or in combination, altered the locomotor activity of mice. I.c.v. administration of MPP(+) increased the striatal immunocontent of TH, an effect prevented by the three tested doses of agmatine. MPP(+) and agmatine did not alter the immunocontent of BDNF in striatum and frontal cortex. These results demonstrate for the first time the antidepressant-like effects of agmatine in an animal model of depressive-like behavior induced by the dopaminergic neurotoxin MPP(+).
authors.affiliation: Department of Pharmacology, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, SC, 88049-900, Brazil, morganamoretti@hotmail.com.
authors.forename: Morgana
authors.initials: M
authors.lastname: Moretti
authors.forename: Vivian Binder
authors.initials: VB
authors.lastname: Neis
authors.forename: Filipe Carvalho
authors.initials: FC
authors.lastname: Matheus
authors.forename: Mauricio Peña
authors.initials: MP
authors.lastname: Cunha
authors.forename: Priscila Batista
authors.initials: PB
authors.lastname: Rosa
authors.forename: Camille Mertins
authors.initials: CM
authors.lastname: Ribeiro
authors.forename: Ana Lúcia S
authors.initials: AL
authors.lastname: Rodrigues
authors.forename: Rui Daniel
authors.initials: RD
authors.lastname: Prediger
mesh_terms: D000376:Agmatine / Q000494:pharmacology*; D059445:Anhedonia / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D003866:Depressive Disorder / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D020267:MPTP Poisoning / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology; D008297:Male; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D000376:Agmatine; D014446:Tyrosine 3-Monooxygenase