Evidence map›Paper›PMID 31267156›Full record

ArticlePsychopharmacology2019

NMDA receptor antagonists traxoprodil and lanicemine improve hippocampal-prefrontal coupling and reward-related networks in rats.

Robert Becker, Natalia Gass, Lothar Kußmaul, Bernhard Schmid, Stefan Scheuerer, David Schnell, Cornelia Dorner-Ciossek, Wolfgang Weber-Fahr, Alexander Sartorius

Abstract read
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In one paragraph

Article in Psychopharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Mechanisms of Transmission and Processing of Pain: A Narrative Review.International journal of environmental research and public health · 2023
    Review
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

9 authors.

Robert BeckerResearch Group Translational Imaging, Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159, Mannheim, Germany. robert.becker@zi-mannheim.de.ORCID http://orcid.org/0000-0003-4080-4452
Natalia GassResearch Group Translational Imaging, Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159, Mannheim, Germany.
Lothar KußmaulBoehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Bernhard SchmidBoehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Stefan ScheuererBoehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
David SchnellBoehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Cornelia Dorner-CiossekBoehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Wolfgang Weber-FahrResearch Group Translational Imaging, Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159, Mannheim, Germany.
Alexander SartoriusResearch Group Translational Imaging, Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159, Mannheim, Germany.

Funding

Deutsche Forschungsgemeinschaft GA 2109/2-1Deutsche Forschungsgemeinschaft SA 1869/11-2Deutsche Forschungsgemeinschaft SA 1869/14-1
6 · The paper itself

Abstract

rationaleThe N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine is known to have not only a rapid antidepressant effect but also dissociative side effects. Traxoprodil and lanicemine, also NMDA antagonists, are candidate antidepressant drugs with fewer side effects.

objectivesIn order to understand their mechanism of action, we investigated the acute effects of traxoprodil and lanicemine on brain connectivity using resting-state functional magnetic resonance imaging (rs-fMRI).

methodsFunctional connectivity (FC) alterations were examined using interregional correlation networks. Graph theoretical methods were used for whole brain network analysis. As interest in NMDAR antagonists as potential antidepressants was triggered by the antidepressant effect of ketamine, results were compared to previous findings from our ketamine studies.

resultsSimilar to ketamine but to a smaller extent, traxoprodil increased hippocampal-prefrontal (Hc-PFC) coupling. Unlike ketamine, traxoprodil decreased connectivity within the PFC. Lanicemine had no effect on these properties. The improvement of Hc-PFC coupling corresponds well to clinical result, showing ketamine to have a greater antidepressant effect than traxoprodil, while lanicemine has a weak and transient effect. Connectivity changes overlapping between the drugs as well as alterations of local network properties occurred mostly in reward-related regions.

conclusionThe antidepressant effect of NMDA antagonists appears to be associated with enhanced Hc-PFC coupling. The effects on local network properties and regional connectivity suggest that improvement of reward processing might also be important for understanding the mechanisms underlying the antidepressant effects of these drugs.

Indexed as

RewardAnimalsAntidepressive AgentsExcitatory Amino Acid AntagonistsHippocampusMagnetic Resonance ImagingMalePhenethylaminesPiperidinesPrefrontal CortexPyridinesRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateAntidepressive AgentsAZD6765Excitatory Amino Acid AntagonistsPhenethylaminesPiperidinesPyridinesReceptors, N-Methyl-D-Aspartatetraxoprodil mesylatefMRIHippocampal-prefrontal couplingNetworksNMDA antagonists

Identifiers

PMID31267156

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Registered trials

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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.