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Pharmacol Biochem Behav. 2014 Jul;122:53-60. doi: 10.1016/j.pbb.2014.03.008. Epub 2014 Mar 18.

Antidepressant-like effect of Canavalia brasiliensis (ConBr) lectin in mice: evidence for the involvement of the glutamatergic system.

Author information

1
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil.
2
BioMolLab, Universidade Federal do Ceará, Fortaleza, CE 60455-970, Brazil.
3
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil. Electronic address: rbleal@gmail.com.

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.

KEYWORDS:

ConBr; Depression; Forced swimming test; Lectin; NMDA; Nitric oxide

PMID:
24650588
DOI:
10.1016/j.pbb.2014.03.008
[Indexed for MEDLINE]

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