Vortioxetine (Lu AA21004), a novel multimodal antidepressant, enhances memory in rats

Arne Mørk, Liliana P. Montezinho, Silke Miller, Crista Trippodi-Murphy, Niels Plath, Yan Li, Maria E. Gulinello, Connie Sanchez

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

The serotonergic system plays an important role in cognitive functions via various 5-HT receptors. Vortioxetine (Lu AA21004) in development as a novel multimodal antidepressant is a 5-HT3, 5-HT7 and 5-HT 1D receptor antagonist, a 5-HT1B receptor partial agonist, a 5-HT1A receptor agonist and a 5-HT transporter (5-HTT) inhibitor in vitro. Preclinical studies suggest that 5-HT3 and 5-HT7 receptor antagonism as well as 5-HT1A receptor agonism may have a positive impact on cognitive functions including memory. Thus vortioxetine may potentially enhance memory. We investigated preclinical effects of vortioxetine (1-10 mg/kg administered subcutaneously [s.c.]) on memory in behavioral tests, and on cortical neurotransmitter levels considered important in rat memory function. Contextual fear conditioning and novel object recognition tests were applied to assess memory in rats. Microdialysis studies were conducted to measure extracellular neurotransmitter levels in the rat medial prefrontal cortex. Vortioxetine administered 1 h before or immediately after acquisition of contextual fear conditioning led to an increase in freezing time during the retention test. This mnemonic effect was not related to changes in pain sensitivity as measured in the hotplate test. Rats treated with vortioxetine 1 h before training spent more time exploring the novel object in the novel object recognition test. In microdialysis studies of the rat medial prefrontal cortex, vortioxetine increased extracellular levels of acetylcholine and histamine. In conclusion, vortioxetine enhanced contextual and episodic memory in rat behavioral models. Further demonstration of its potential effect on memory functions in clinical settings is warranted.

Original languageEnglish (US)
Pages (from-to)41-50
Number of pages10
JournalPharmacology Biochemistry and Behavior
Volume105
DOIs
StatePublished - Apr 2013

Fingerprint

Antidepressive Agents
Rats
Data storage equipment
Receptor, Serotonin, 5-HT1A
Microdialysis
Object recognition
Prefrontal Cortex
Cognition
Fear
Neurotransmitter Agents
Receptor, Serotonin, 5-HT1D
Receptor, Serotonin, 5-HT1B
Serotonin 5-HT1 Receptor Agonists
Episodic Memory
vortioxetine
Serotonin Receptors
Freezing
Histamine
Acetylcholine
Serotonin

Keywords

  • Acetylcholine
  • Cognitive dysfunction
  • Memory
  • Multimodal
  • Serotonin
  • Vortioxetine

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Pharmacology
  • Toxicology
  • Behavioral Neuroscience
  • Biological Psychiatry

Cite this

Mørk, A., Montezinho, L. P., Miller, S., Trippodi-Murphy, C., Plath, N., Li, Y., ... Sanchez, C. (2013). Vortioxetine (Lu AA21004), a novel multimodal antidepressant, enhances memory in rats. Pharmacology Biochemistry and Behavior, 105, 41-50. https://doi.org/10.1016/j.pbb.2013.01.019

Vortioxetine (Lu AA21004), a novel multimodal antidepressant, enhances memory in rats. / Mørk, Arne; Montezinho, Liliana P.; Miller, Silke; Trippodi-Murphy, Crista; Plath, Niels; Li, Yan; Gulinello, Maria E.; Sanchez, Connie.

In: Pharmacology Biochemistry and Behavior, Vol. 105, 04.2013, p. 41-50.

Research output: Contribution to journalArticle

Mørk, Arne ; Montezinho, Liliana P. ; Miller, Silke ; Trippodi-Murphy, Crista ; Plath, Niels ; Li, Yan ; Gulinello, Maria E. ; Sanchez, Connie. / Vortioxetine (Lu AA21004), a novel multimodal antidepressant, enhances memory in rats. In: Pharmacology Biochemistry and Behavior. 2013 ; Vol. 105. pp. 41-50.
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