Involvement of kynurenine pathway and N-methyl-d-aspartate receptors in the antidepressant-like effect of vilazodone in the tail suspension test in mice

The present study evaluated the antidepressant-like effects of vilazodone using the tail suspension test in mice. We also investigated the contribution of kynurenine pathway and N-methyl-d-aspartate receptors to this effect. For this purpose, we pretreated animals with sub-effective doses of L-kynur...

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Published in:	Pharmacology, biochemistry and behavior Vol. 218; p. 173433
Main Authors:	de Arruda, Cristina Maria, Doneda, Diego Luiz, de Oliveira, Vinícius Vezzi, da Silva, Rozielly Aparecida Lemes, de Matos, Yohan Alves Victor, Fernandes, Isadora Luiza, Rohden, Christopher Alecsander Herane, Viola, Giordano Gubert, Rios-Santos, Fabrício, de Lima, Eliângela, da Silva Buss, Ziliani, Vandresen-Filho, Samuel
Format:	Journal Article
Language:	English
Published:	Elsevier Inc 01-07-2022
Subjects:	3-hydroxykynurenine Antidepressant Depressive-like behavior Ketamine L-kynurenine N-methyl-d-aspartate NMDA Quinolinic acid Serotonin Tail suspension test Antidepressant N-methyl-d-aspartate 3-hydroxykynurenine Ketamine Serotonin Depressive-like behavior NMDA L-kynurenine Quinolinic acid Tail suspension test
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Summary:	The present study evaluated the antidepressant-like effects of vilazodone using the tail suspension test in mice. We also investigated the contribution of kynurenine pathway and N-methyl-d-aspartate receptors to this effect. For this purpose, we pretreated animals with sub-effective doses of L-kynurenine, 3-hydroxykynurenine, or quinolinic acid. We then assessed the immobility time, an indicative measure of depressive-like behavior, in the tail suspension test. We also evaluated the possible effects of sub-effective doses of vilazodone combined with sub-effective doses of ketamine (N-methyl-d-aspartate receptor antagonist) in a separate group. Vilazodone (3mg/kg, intraperitoneal) significantly reduced immobility time in the tail suspension test. L-kynurenine (1.7 mg/kg, intraperitoneal), 3-hydroxykynurenine (10 mg/kg, intraperitoneal), and quinolinic acid (3 nmol/site, intracerebroventricular) significantly increased the immobility time in the tail suspension test. The antidepressant-like effects of vilazodone (3mg/kg, intraperitoneal) were inhibited by pre-treatment with non-effective doses of L-kynurenine (0.83 mg/kg, intraperitoneal), 3-hydroxykynurenine (3.33 mg/kg, intraperitoneal), or quinolinic acid (1 nmol/site, intracerebroventricular). Pretreatment of mice with sub-effective doses of ketamine (1 mg/kg, intraperitoneal) optimized the action of a sub-effective dose of vilazodone (0.3mg/kg, intraperitoneal) and reduced the immobility time in the tail suspension test. None of the drugs used in this study induced any changes in locomotor activity in the open field test. The results showed that vilazodone induced an antidepressant-like effect in the tail suspension test, which may be mediated through an interaction with the kynurenine pathway and N-methyl-d-aspartate receptors. •Vilazodone (VZD) has an antidepressant-like effect in TST.•Metabolites of the kynurenine pathway increased immobility time of mice in TST.•Metabolites of the kynurenine pathway prevented the anti-immobility effect of VZD.•Ketamine potentiated the effect of VZD in TST.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0091-3057 1873-5177
DOI:	10.1016/j.pbb.2022.173433