Evidence map›Paper›PMID 27402279›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2016

Task- and Treatment Length-Dependent Effects of Vortioxetine on Scopolamine-Induced Cognitive Dysfunction and Hippocampal Extracellular Acetylcholine in Rats.

Alan L Pehrson, Todd M Hillhouse, Nasser Haddjeri, Renaud Rovera, Joseph H Porter, Arne Mørk, Gennady Smagin, Dekun Song, David Budac, Manuel Cajina and 1 more

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In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Use of vortioxetine in different neurological fields: a systematic review and future perspectives.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
    Pooled it
  2. Review
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  5. In vivo electrophysiological study of the targeting of 5-HTThe European journal of neuroscience · 2022
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  7. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Alan L PehrsonLundbeck Research USA, Paramus, New Jersey (A.L.P., G.S., D.S., D.B., M.C., C.S.); Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark (C.S.); Department of Pharmacology, University of Michigan, Ann Arbor, Michigan (T.M.H.); Psychology Department, Virginia Commonwealth University, Richmond, Virginia (T.M.H., J.H.P.); Univ Lyon, Université Claude Bernard Lyon 1, Inserm, Stem Cell and Brain Research Institute U1208, 69500 Bron, France (R.R., N.H.); and H. Lundbeck A/S, Copenhagen-Valby, Denmark (A.M.).ORCID 0000-0002-0470-0202
Todd M HillhouseLundbeck Research USA, Paramus, New Jersey (A.L.P., G.S., D.S., D.B., M.C., C.S.); Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark (C.S.); Department of Pharmacology, University of Michigan, Ann Arbor, Michigan (T.M.H.); Psychology Department, Virginia Commonwealth University, Richmond, Virginia (T.M.H., J.H.P.); Univ Lyon, Université Claude Bernard Lyon 1, Inserm, Stem Cell and Brain Research Institute U1208, 69500 Bron, France (R.R., N.H.); and H. Lundbeck A/S, Copenhagen-Valby, Denmark (A.M.).
Nasser HaddjeriLundbeck Research USA, Paramus, New Jersey (A.L.P., G.S., D.S., D.B., M.C., C.S.); Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark (C.S.); Department of Pharmacology, University of Michigan, Ann Arbor, Michigan (T.M.H.); Psychology Department, Virginia Commonwealth University, Richmond, Virginia (T.M.H., J.H.P.); Univ Lyon, Université Claude Bernard Lyon 1, Inserm, Stem Cell and Brain Research Institute U1208, 69500 Bron, France (R.R., N.H.); and H. Lundbeck A/S, Copenhagen-Valby, Denmark (A.M.).
Renaud RoveraLundbeck Research USA, Paramus, New Jersey (A.L.P., G.S., D.S., D.B., M.C., C.S.); Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark (C.S.); Department of Pharmacology, University of Michigan, Ann Arbor, Michigan (T.M.H.); Psychology Department, Virginia Commonwealth University, Richmond, Virginia (T.M.H., J.H.P.); Univ Lyon, Université Claude Bernard Lyon 1, Inserm, Stem Cell and Brain Research Institute U1208, 69500 Bron, France (R.R., N.H.); and H. Lundbeck A/S, Copenhagen-Valby, Denmark (A.M.).
Joseph H PorterLundbeck Research USA, Paramus, New Jersey (A.L.P., G.S., D.S., D.B., M.C., C.S.); Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark (C.S.); Department of Pharmacology, University of Michigan, Ann Arbor, Michigan (T.M.H.); Psychology Department, Virginia Commonwealth University, Richmond, Virginia (T.M.H., J.H.P.); Univ Lyon, Université Claude Bernard Lyon 1, Inserm, Stem Cell and Brain Research Institute U1208, 69500 Bron, France (R.R., N.H.); and H. Lundbeck A/S, Copenhagen-Valby, Denmark (A.M.).
Arne MørkLundbeck Research USA, Paramus, New Jersey (A.L.P., G.S., D.S., D.B., M.C., C.S.); Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark (C.S.); Department of Pharmacology, University of Michigan, Ann Arbor, Michigan (T.M.H.); Psychology Department, Virginia Commonwealth University, Richmond, Virginia (T.M.H., J.H.P.); Univ Lyon, Université Claude Bernard Lyon 1, Inserm, Stem Cell and Brain Research Institute U1208, 69500 Bron, France (R.R., N.H.); and H. Lundbeck A/S, Copenhagen-Valby, Denmark (A.M.).
Gennady SmaginLundbeck Research USA, Paramus, New Jersey (A.L.P., G.S., D.S., D.B., M.C., C.S.); Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark (C.S.); Department of Pharmacology, University of Michigan, Ann Arbor, Michigan (T.M.H.); Psychology Department, Virginia Commonwealth University, Richmond, Virginia (T.M.H., J.H.P.); Univ Lyon, Université Claude Bernard Lyon 1, Inserm, Stem Cell and Brain Research Institute U1208, 69500 Bron, France (R.R., N.H.); and H. Lundbeck A/S, Copenhagen-Valby, Denmark (A.M.).
Dekun SongLundbeck Research USA, Paramus, New Jersey (A.L.P., G.S., D.S., D.B., M.C., C.S.); Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark (C.S.); Department of Pharmacology, University of Michigan, Ann Arbor, Michigan (T.M.H.); Psychology Department, Virginia Commonwealth University, Richmond, Virginia (T.M.H., J.H.P.); Univ Lyon, Université Claude Bernard Lyon 1, Inserm, Stem Cell and Brain Research Institute U1208, 69500 Bron, France (R.R., N.H.); and H. Lundbeck A/S, Copenhagen-Valby, Denmark (A.M.).
David BudacLundbeck Research USA, Paramus, New Jersey (A.L.P., G.S., D.S., D.B., M.C., C.S.); Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark (C.S.); Department of Pharmacology, University of Michigan, Ann Arbor, Michigan (T.M.H.); Psychology Department, Virginia Commonwealth University, Richmond, Virginia (T.M.H., J.H.P.); Univ Lyon, Université Claude Bernard Lyon 1, Inserm, Stem Cell and Brain Research Institute U1208, 69500 Bron, France (R.R., N.H.); and H. Lundbeck A/S, Copenhagen-Valby, Denmark (A.M.).
Manuel CajinaLundbeck Research USA, Paramus, New Jersey (A.L.P., G.S., D.S., D.B., M.C., C.S.); Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark (C.S.); Department of Pharmacology, University of Michigan, Ann Arbor, Michigan (T.M.H.); Psychology Department, Virginia Commonwealth University, Richmond, Virginia (T.M.H., J.H.P.); Univ Lyon, Université Claude Bernard Lyon 1, Inserm, Stem Cell and Brain Research Institute U1208, 69500 Bron, France (R.R., N.H.); and H. Lundbeck A/S, Copenhagen-Valby, Denmark (A.M.).
Connie SanchezLundbeck Research USA, Paramus, New Jersey (A.L.P., G.S., D.S., D.B., M.C., C.S.); Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark (C.S.); Department of Pharmacology, University of Michigan, Ann Arbor, Michigan (T.M.H.); Psychology Department, Virginia Commonwealth University, Richmond, Virginia (T.M.H., J.H.P.); Univ Lyon, Université Claude Bernard Lyon 1, Inserm, Stem Cell and Brain Research Institute U1208, 69500 Bron, France (R.R., N.H.); and H. Lundbeck A/S, Copenhagen-Valby, Denmark (A.M.) connie_sanchez@clin.au.dk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Major depressive disorder (MDD) is a common psychiatric disorder that often features impairments in cognitive function, and these cognitive symptoms can be important determinants of functional ability. Vortioxetine is a multimodal antidepressant that may improve some aspects of cognitive function in patients with MDD, including attention, processing speed, executive function, and memory. However, the cause of these effects is unclear, and there are several competing theories on the underlying mechanism, notably including regionally-selective downstream enhancement of glutamate neurotransmission and increased acetylcholine (ACh) neurotransmission. The current work sought to evaluate the ACh hypothesis by examining vortioxetine's ability to reverse scopolamine-induced impairments in rodent tests of memory and attention. Additionally, vortioxetine's effects on hippocampal extracellular ACh levels were examined alongside studies of vortioxetine's pharmacokinetic profile. We found that acute vortioxetine reversed scopolamine-induced impairments in social and object recognition memory, but did not alter scopolamine-induced impairments in attention. Acute vortioxetine also induced a modest and short-lived increase in hippocampal ACh levels. However, this short-term effect is at variance with vortioxetine's moderately long brain half life (5.1 hours). Interestingly, subchronic vortioxetine treatment failed to reverse scopolamine-induced social recognition memory deficits and had no effects on basal hippocampal ACh levels. These data suggest that vortioxetine has some effects on memory that could be mediated through cholinergic neurotransmission, however these effects are modest and only seen under acute dosing conditions. These limitations may argue against cholinergic mechanisms being the primary mediator of vortioxetine's cognitive effects, which are observed under chronic dosing conditions in patients with MDD.

Indexed as

AcetylcholineAnimalsCognitive DysfunctionExtracellular SpaceHippocampusMalePiperazinesRatsRats, WistarRecognition, PsychologyScopolamineSocial BehaviorSulfidesSynaptic TransmissionVortioxetineAcetylcholinePiperazinesScopolamineSulfidesVortioxetine

Identifiers

PMID27402279
PMCPMC4998672

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.