title: Antidepressant-like action of the bark ethanolic extract from Tabebuia avellanedae in the olfactory bulbectomized mice.
abstract: BACKGROUND
  Tabebuia avellanedae Lorentz ex Griseb is a plant employed in tropical America folk medicine for the treatment of several diseases, including depressive disorders.
  
  
  OBJECTIVE
  To investigate the ability of Tabebuia avellanedae ethanolic extract (EET) administered chronically to cause an antidepressant-like effect in the tail suspension test (TST), a predictive test of antidepressant activity, and to reverse behavioral (hyperactivity, anhedonic-like behavior and increased immobility time in the TST) and biochemical changes induced by olfactory bulbectomy (OB), a model of depression, in mice.
  
  
  METHODS
  Mice were submitted to OB to induce depressive-related behaviors, which were evaluated in the open-field test (hyperactivity), splash test (loss of motivational and self-care behavior indicative of an anhedonic-like behavior) and TST (increased immobility time). Phosphorylation levels of Akt, GSK-3β, ERK1/2 and CREB, as well as BDNF immunocontent, were evaluated in the hippocampus of bulbectomized mice or sham-operated mice treated for 14 days by p.o. route with EET or vehicle.
  
  
  RESULTS
  EET (10 and 30mg/kg) given 14 days by p.o route to mice reduced the immobility time in the TST without altering locomotor activity, an indicative of an antidepressant-like effect. EET per se increased both CREB (Ser(133)) and GSK-3β (Ser(9)) phosphorylation (at doses of 10-30 and 30mg/kg, respectively) in sham-operated mice. OB caused hyperactivity, loss of motivational and self-care behavior, increased immobility time in the TST and an increase in CREB and ERK1 phosphorylation, as well as BDNF immunocontent. EET abolished all these OB-induced alterations except the increment of CREB phosphorylation. Akt (Ser(473)) and ERK2 phosphorylation levels were not altered in any group.
  
  
  CONCLUSIONS
  EET ability to abolish the behavioral changes induced by OB was accompanied by modulation of ERK1 and BDNF signaling pathways, being a promising target of EET. Results indicate that this plant could constitute an attractive strategy for the management of depressive disorders, once more validating the traditional use of this plant.
authors.affiliation: Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário-Trindade, 88040-900 Florianópolis-SC, Brazil.
authors.forename: Andiara E
authors.initials: AE
authors.lastname: Freitas
authors.forename: Daniele G
authors.initials: DG
authors.lastname: Machado
authors.forename: Josiane
authors.initials: J
authors.lastname: Budni
authors.forename: Vivian B
authors.initials: VB
authors.lastname: Neis
authors.forename: Grasiela O
authors.initials: GO
authors.lastname: Balen
authors.forename: Mark W
authors.initials: MW
authors.lastname: Lopes
authors.forename: Luiz F
authors.initials: LF
authors.lastname: de Souza
authors.forename: Patricia O
authors.initials: PO
authors.lastname: Veronezi
authors.forename: Melina
authors.initials: M
authors.lastname: Heller
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Micke
authors.forename: Moacir G
authors.initials: MG
authors.lastname: Pizzolatti
authors.forename: Alcir L
authors.initials: AL
authors.lastname: Dafre
authors.forename: Rodrigo B
authors.initials: RB
authors.lastname: Leal
authors.forename: Ana Lúcia S
authors.initials: AL
authors.lastname: Rodrigues
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D050882:CREB-Binding Protein / Q000378:metabolism; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000431:Ethanol / Q000737:chemistry; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009830:Olfactory Bulb / Q000601:surgery; D008517:Phytotherapy; D024301:Plant Bark; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012997:Solvents / Q000737:chemistry; D029663:Tabebuia
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D010936:Plant Extracts; D012997:Solvents; D000431:Ethanol; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D038362:Glycogen Synthase Kinase 3