NMDA receptors and the L-arginine-nitric oxide-cyclic guanosine monophosphate pathway are implicated in the antidepressant-like action of the ethanolic extract from Tabebuia avellanedae in mice.
Bark infusion of Tabebuia avellanedae Lorentz ex Griseb is consumed in tropical America folk medicine for the treatment of several diseases, including depressive disorders. It was recently demonstrated that the extract from this plant has antidepressant properties. The present study was aimed at investigating the contribution of N-methyl-D-aspartate (NMDA) receptors and the L-arginine-nitric oxide (NO)-cyclic guanosine 3'5'-monophosphate (cGMP) pathway to the antidepressant-like action of the ethanolic extract from T. avellanedae (EET) in the tail suspension test (TST). The anti-immobility effect of the extract (30 mg/kg, orally [p.o.]) was prevented by pretreatment of mice with NMDA (0.1 pmol/site, intracerebroventicular [i.c.v.]), L-arginine (750 mg/kg, intraperitoneally [i.p.]), and sildenafil (5 mg/kg, i.p.). Additionally, the combination of MK-801 (0.01 mg/kg, p.o.), 7-nitroindazole (25 mg/kg, i.p.), and 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ) (30 pmol/site, i.c.v.) with a subeffective dose of EET (1 mg/kg, p.o.) produced a synergistic antidepressant-like effect in the TST, without causing significant alterations in the locomotor activity. Moreover, the administration of an effective dose of EET (30 mg/kg, p.o.) produced a reduction in NOx levels in the cerebral cortex. Conversely, a subeffective dose of EET (1 mg/kg, p.o.) caused no changes in the cortical NOx levels. Results suggest that the antidepressant-like effect of EET in the TST is dependent on a blockade of NMDA receptor activation and inhibition of NO-cGMP synthesis, significantly extending literature data about the antidepressant-like action of this plant and reinforcing the notion that this plant may be useful in the management of depressive disorders.
1 Department of Biochemistry, Center of Biological Sciences, Federal University of Santa Catarina , Florianópolis, Santa Catarina, Brazil .
Andiara E
AE
Freitas
Morgana
M
Moretti
Josiane
J
Budni
Grasiela O
GO
Balen
Sinara C
SC
Fernandes
Patricia O
PO
Veronezi
Melina
M
Heller
Gustavo A
GA
Micke
Moacir G
MG
Pizzolatti
Ana Lúcia S
AL
Rodrigues
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001120:Arginine / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects; D003863:Depression / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006157:Guanosine Monophosphate / Q000378:metabolism*; D019417:Hindlimb Suspension; D008124:Locomotion / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D009569:Nitric Oxide / Q000378:metabolism*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015398:Signal Transduction; D029663:Tabebuia
D000928:Antidepressive Agents; D010936:Plant Extracts; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D006157:Guanosine Monophosphate; D001120:Arginine