Effects of vortioxetine on biomarkers associated with glutamatergic activity in an SSRI insensitive model of depression in female rats.
Prog Neuropsychopharmacol Biol Psychiatry
; 82: 332-338, 2018 03 02.
Article
en En
| MEDLINE
| ID: mdl-29269186
ABSTRACT
The aim of this study was to investigate the antidepressant activity of vortioxetine in a tryptophan (TRP) depletion female rat model of depression and compare it to that of paroxetine using doses that fully occupy the serotonin transporter (SERT). We evaluated the effects of vortioxetine on potential biomarkers associated with TRP depletion including serum aldosterone, corticosterone and IL-6 levels together with indirect indicators of glutamate neurotransmission. Female Sprague-Dawley rats were randomized to control, low TRP, low TRP/paroxetine or low TRP/vortioxetine groups. Vortioxetine and paroxetine were administered via diet (10mg/kg/day) and drinking water (10mg/kg/day) respectively for 14days. Vortioxetine but not paroxetine reversed TRP depletion-induced depressive-like behavior. Vortioxetine reduced TRP depletion-induced increases of serum corticosterone, aldosterone, IL-6 and N-methyl-d-aspartate and α7-nicotinic acetylcholine receptor expression in the amygdala and hippocampus, respectively. Paroxetine demonstrated little effect except a reduction of aldosterone. Vortioxetine but not paroxetine reversed TRP depletion-induced reductions of serum and brain kynurenic acid. In conclusion, vortioxetine, but not paroxetine, enabled reversals of TRP depletion-induced changes of depression-like behavior and markers of glutamatergic activity. These observations support the hypothesis that vortioxetine's antidepressant activity may involve mechanisms beyond SERT inhibition.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Inhibidores Selectivos de la Recaptación de Serotonina
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Ácido Glutámico
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Trastorno Depresivo
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Vortioxetina
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Prog Neuropsychopharmacol Biol Psychiatry
Año:
2018
Tipo del documento:
Article
País de afiliación:
Eslovaquia