Behavioral and neurochemical effects of folic acid in a mouse model of depression induced by TNF-α.
Behav Brain Res
; 414: 113512, 2021 09 24.
Article
en En
| MEDLINE
| ID: mdl-34358572
Folic acid has been reported to exert antidepressant effects, but its ability to abrogate the depressive-like behavior and signaling pathways alterations elicited by an inflammatory model of depression remains to be established. This study examined: a) the efficacy of folic acid in a mouse model of depression induced by tumor necrosis factor (TNF-α); b) whether the administration of subthreshold doses of folic acid and antidepressants (fluoxetine, imipramine, and bupropion), MK-801, or 7-nitroindazole cause antidepressant-like effects; c) the effects of TNF-α and/or folic acid on hippocampal p38MAPK, Akt, ERK, and JNK phosphorylation. Folic acid reduced the immobility time in the tail suspension test (TST) in control mice (10-50 mg/kg, p.o) and abolished the depressive-like behavior elicited by TNF-α (0.001 fg/site, i.c.v.) in this test (1-50 mg/kg, p.o). Coadministration of subthreshold doses of folic acid (1 mg/kg, p.o.) and fluoxetine, imipramine, bupropion, MK-801, or 7-nitroindazole produced an antidepressant-like effect in mice exposed or not to TNF-α. TNF-α-treated mice presented increased p38MAPK phosphorylation and decreased Akt phosphorylation, and the later effect was prevented by folic acid (10 mg/kg, p.o.). Additionally, ERK1 phosphorylation was increased in mice treated with TNF-α + folic acid (1 mg/kg), but no effects on ERK2 or JNK1/2/3 phosphorylation were found in any group. The results indicate the efficacy of folic acid to counteract the depressive-like behavior induced by a pro-inflammatory cytokine, an effect that might be associated with the activation of monoaminergic systems, inhibition of N-methyl-d-aspartate (NMDA) receptors and nitric oxide (NO) synthesis, as well as Akt modulation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Complejo Vitamínico B
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Conducta Animal
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Factor de Necrosis Tumoral alfa
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Depresión
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Ácido Fólico
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Antidepresivos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Behav Brain Res
Año:
2021
Tipo del documento:
Article
País de afiliación:
Brasil
Pais de publicación:
Países Bajos