Effect of the multimodal acting antidepressant vortioxetine on rat hippocampal plasticity and recognition memory

Cécile Bétry, Adeline Etiévant, Alan Pehrson, Connie Sánchez, Nasser Haddjeri

Research output: Contribution to journalArticleResearchpeer-review

29 Citations (Scopus)

Abstract

Depression is frequently associated with cognitive disturbances. Vortioxetine is a multimodal acting antidepressant that functions as a 5-HT3 and 5-HT7 and 5-HT1D receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist and inhibitor of the 5-HT transporter. Given its pharmacological profile, the present study was undertaken to determine whether vortioxetine could modulate several preclinical parameters known to be involved in cognitive processing.In the dorsal hippocampus of anaesthetized rats, the high-frequency stimulation of the Schaffer collaterals provoked a stable long-term potentiation (LTP) of ~25%. Interestingly, vortioxetine (10mg/kg, i.p.) counteracted the suppressant effect of elevated platform stress on hippocampal LTP induction. In the novel object recognition test, vortioxetine (10mg/kg, i.p.) increased the time spent exploring the novel object during the retention test and this pro-cognitive effect was prevented by the partial 5-HT3 receptor agonist SR57227 (1mg/kg, i.p.). Finally, compared to fluoxetine, sustained administration of vortioxetine (5mg/kg/day, s.c.) induced a rapid increase of cell proliferation in the hippocampal dentate gyrus.In summary, vortioxetine prevented the effect of stress on hippocampal LTP, increased rapidly hippocampal cell proliferation and enhanced short-term episodic memory, via, at least in part, its 5-HT3 receptor antagonism. Taken together, these preclinical data suggest that the antidepressant vortioxetine may have a beneficial effect on human cognitive processes.

Original languageEnglish
Pages (from-to)38-46
Number of pages9
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume58
DOIs
StatePublished - 3 Apr 2015

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Antidepressive Agents
Long-Term Potentiation
Receptors, Serotonin, 5-HT3
Hippocampus
Serotonin 5-HT3 Receptor Agonists
Receptor, Serotonin, 5-HT1D
Cell Proliferation
Serotonin 5-HT1 Receptor Antagonists
Receptor, Serotonin, 5-HT1B
Serotonin 5-HT1 Receptor Agonists
Parahippocampal Gyrus
Receptor, Serotonin, 5-HT1A
Episodic Memory
Fluoxetine
Dentate Gyrus
vortioxetine
Recognition (Psychology)
Short-Term Memory
Serotonin
Pharmacology

Keywords

  • Antidepressant
  • LTP
  • Memory
  • Neurogenesis
  • Novel object recognition
  • Vortioxetine

Cite this

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title = "Effect of the multimodal acting antidepressant vortioxetine on rat hippocampal plasticity and recognition memory",
abstract = "Depression is frequently associated with cognitive disturbances. Vortioxetine is a multimodal acting antidepressant that functions as a 5-HT3 and 5-HT7 and 5-HT1D receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist and inhibitor of the 5-HT transporter. Given its pharmacological profile, the present study was undertaken to determine whether vortioxetine could modulate several preclinical parameters known to be involved in cognitive processing.In the dorsal hippocampus of anaesthetized rats, the high-frequency stimulation of the Schaffer collaterals provoked a stable long-term potentiation (LTP) of ~25{\%}. Interestingly, vortioxetine (10mg/kg, i.p.) counteracted the suppressant effect of elevated platform stress on hippocampal LTP induction. In the novel object recognition test, vortioxetine (10mg/kg, i.p.) increased the time spent exploring the novel object during the retention test and this pro-cognitive effect was prevented by the partial 5-HT3 receptor agonist SR57227 (1mg/kg, i.p.). Finally, compared to fluoxetine, sustained administration of vortioxetine (5mg/kg/day, s.c.) induced a rapid increase of cell proliferation in the hippocampal dentate gyrus.In summary, vortioxetine prevented the effect of stress on hippocampal LTP, increased rapidly hippocampal cell proliferation and enhanced short-term episodic memory, via, at least in part, its 5-HT3 receptor antagonism. Taken together, these preclinical data suggest that the antidepressant vortioxetine may have a beneficial effect on human cognitive processes.",
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Effect of the multimodal acting antidepressant vortioxetine on rat hippocampal plasticity and recognition memory. / Bétry, Cécile; Etiévant, Adeline; Pehrson, Alan; Sánchez, Connie; Haddjeri, Nasser.

In: Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 58, 03.04.2015, p. 38-46.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Effect of the multimodal acting antidepressant vortioxetine on rat hippocampal plasticity and recognition memory

AU - Bétry, Cécile

AU - Etiévant, Adeline

AU - Pehrson, Alan

AU - Sánchez, Connie

AU - Haddjeri, Nasser

PY - 2015/4/3

Y1 - 2015/4/3

N2 - Depression is frequently associated with cognitive disturbances. Vortioxetine is a multimodal acting antidepressant that functions as a 5-HT3 and 5-HT7 and 5-HT1D receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist and inhibitor of the 5-HT transporter. Given its pharmacological profile, the present study was undertaken to determine whether vortioxetine could modulate several preclinical parameters known to be involved in cognitive processing.In the dorsal hippocampus of anaesthetized rats, the high-frequency stimulation of the Schaffer collaterals provoked a stable long-term potentiation (LTP) of ~25%. Interestingly, vortioxetine (10mg/kg, i.p.) counteracted the suppressant effect of elevated platform stress on hippocampal LTP induction. In the novel object recognition test, vortioxetine (10mg/kg, i.p.) increased the time spent exploring the novel object during the retention test and this pro-cognitive effect was prevented by the partial 5-HT3 receptor agonist SR57227 (1mg/kg, i.p.). Finally, compared to fluoxetine, sustained administration of vortioxetine (5mg/kg/day, s.c.) induced a rapid increase of cell proliferation in the hippocampal dentate gyrus.In summary, vortioxetine prevented the effect of stress on hippocampal LTP, increased rapidly hippocampal cell proliferation and enhanced short-term episodic memory, via, at least in part, its 5-HT3 receptor antagonism. Taken together, these preclinical data suggest that the antidepressant vortioxetine may have a beneficial effect on human cognitive processes.

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JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry

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