title: Antidepressant-like effect of Canavalia brasiliensis (ConBr) lectin in mice: evidence for the involvement of the glutamatergic system.
abstract: Lectins recognize and reversibly bind to carbohydrates attached to proteins and lipids modulating a variety of signaling pathways. We previously showed that ConBr, a lectin from Canavalia brasiliensis seeds, produced an antidepressant-like effect in mice by modulating the monoaminergic neurotransmitter systems. Moreover, ConBr blocked hippocampal neurotoxicity induced by quinolinic acid in vivo and by glutamate in vitro, suggesting a neuroprotective activity of ConBr via glutamatergic system modulation. Therefore, the present study was undertaken to investigate the involvement of the N-methyl-D-aspartate (NMDA) receptor and the L-arginine-nitric oxide (NO) pathway in the antidepressant-like action displayed by ConBr in the forced swimming test (FST). With the aim of verifying the involvement of NMDA receptors in the antidepressant-like effect of ConBr (10 μg/site, i.c.v.), an intracerebroventricular (i.c.v.) pretreatment with either NMDA (0.1 pmol/site) or D-serine (30 μg/site) was carried out. The results show that both treatments blocked the effect of ConBr. Furthermore, the coadministration of subeffective doses of the NMDA receptor antagonist MK-801 (0.001 mg/kg, i.p.) or ketamine (0.1 mg/kg, i.p.; NMDA receptor antagonist) and ConBr (0.1 μg/site, i.c.v.) caused a synergistic reduction in immobility time. In order to verify the dependence of the L-arginine-NO-cGMP pathway, on the effect of ConBr in the FST, a pretreatment with the NO precursor, L-arginine (750 mg/kg, i.p.), or the PDE5 inhibitor, sildenafil (5 mg/kg, i.p.), was performed. Both drugs abolished the antidepressant-like action of ConBr. Finally, the administration of subeffective doses of the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 30 pmol/site, i.c.v.) and ConBr (0.1 μg/site, i.c.v.) produced a synergistic antidepressant-like effect in the FST. Taken together, the results suggest that the antidepressant-like effect of ConBr in the FST involves NMDA receptor inhibition and reduction in NO and cGMP synthesis.
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil.
authors.forename: Débora K
authors.initials: DK
authors.lastname: Rieger
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Costa
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil.
authors.forename: Josiane
authors.initials: J
authors.lastname: Budni
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil.
authors.forename: Morgana
authors.initials: M
authors.lastname: Moretti
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil.
authors.forename: Sabrina Giovana Rocha
authors.initials: SG
authors.lastname: Barbosa
authors.affiliation: BioMolLab, Universidade Federal do Ceará, Fortaleza, CE 60455-970, Brazil.
authors.forename: Kyria S
authors.initials: KS
authors.lastname: Nascimento
authors.affiliation: BioMolLab, Universidade Federal do Ceará, Fortaleza, CE 60455-970, Brazil.
authors.forename: Edson H
authors.initials: EH
authors.lastname: Teixeira
authors.affiliation: BioMolLab, Universidade Federal do Ceará, Fortaleza, CE 60455-970, Brazil.
authors.forename: Benildo S
authors.initials: BS
authors.lastname: Cavada
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil.
authors.forename: Ana Lúcia S
authors.initials: AL
authors.lastname: Rodrigues
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil. Electronic address: rbleal@gmail.com.
authors.forename: Rodrigo B
authors.initials: RB
authors.lastname: Leal
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000302:isolation & purification / Q000627:therapeutic use*; D032449:Canavalia; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000502:physiology; D008297:Male; D051379:Mice; D010936:Plant Extracts / Q000302:isolation & purification / Q000627:therapeutic use*; D037121:Plant Lectins / Q000302:isolation & purification / Q000627:therapeutic use*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D012639:Seeds; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D010936:Plant Extracts; D037121:Plant Lectins; D016194:Receptors, N-Methyl-D-Aspartate; C039268:lectin, Canavalia; D018698:Glutamic Acid
keywords: ConBr; Depression; Forced swimming test; Lectin; NMDA; Nitric oxide