Effects of vortioxetine on biomarkers associated with glutamatergic activity in an SSRI insensitive model of depression in female rats

N. Hlavacova, Y. Li, Alan Pehrson, C. Sanchez, I. Bermudez, A. Csanova, D. Jezova, M. Franklin

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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 (10 mg/kg/day) and drinking water (10 mg/kg/day) respectively for 14 days. 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.

Original languageEnglish
Pages (from-to)332-338
Number of pages7
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume82
DOIs
StatePublished - 2 Mar 2018

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Paroxetine
Biomarkers
Tryptophan
Depression
Aldosterone
Serotonin Plasma Membrane Transport Proteins
Corticosterone
Antidepressive Agents
Interleukin-6
Serum
Kynurenic Acid
vortioxetine
Nicotinic Receptors
N-Methylaspartate
Amygdala
Synaptic Transmission
Drinking Water
Sprague Dawley Rats
Glutamic Acid
Hippocampus

Keywords

  • Corticosterone
  • Female rat model of depression
  • Glutamatergic system
  • IL-6
  • Tryptophan
  • Vortioxetine

Cite this

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title = "Effects of vortioxetine on biomarkers associated with glutamatergic activity in an SSRI insensitive model of depression in female rats",
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 (10 mg/kg/day) and drinking water (10 mg/kg/day) respectively for 14 days. 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.",
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author = "N. Hlavacova and Y. Li and Alan Pehrson and C. Sanchez and I. Bermudez and A. Csanova and D. Jezova and M. Franklin",
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Effects of vortioxetine on biomarkers associated with glutamatergic activity in an SSRI insensitive model of depression in female rats. / Hlavacova, N.; Li, Y.; Pehrson, Alan; Sanchez, C.; Bermudez, I.; Csanova, A.; Jezova, D.; Franklin, M.

In: Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 82, 02.03.2018, p. 332-338.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Effects of vortioxetine on biomarkers associated with glutamatergic activity in an SSRI insensitive model of depression in female rats

AU - Hlavacova, N.

AU - Li, Y.

AU - Pehrson, Alan

AU - Sanchez, C.

AU - Bermudez, I.

AU - Csanova, A.

AU - Jezova, D.

AU - Franklin, M.

PY - 2018/3/2

Y1 - 2018/3/2

N2 - 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 (10 mg/kg/day) and drinking water (10 mg/kg/day) respectively for 14 days. 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.

AB - 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 (10 mg/kg/day) and drinking water (10 mg/kg/day) respectively for 14 days. 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.

KW - Corticosterone

KW - Female rat model of depression

KW - Glutamatergic system

KW - IL-6

KW - Tryptophan

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U2 - 10.1016/j.pnpbp.2017.07.008

DO - 10.1016/j.pnpbp.2017.07.008

M3 - Article

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SP - 332

EP - 338

JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry

JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry

SN - 0278-5846

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