Oxytocinergic Modulation of Threat-Specific Amygdala Sensitization in Humans Is Critically Mediated by Serotonergic Mechanisms.

Administration, Intranasal Amygdala Emotions Humans Magnetic Resonance Imaging Oxytocin / pharmacology
Amygdala Anxiety Oxytocin Sensitization Serotonin Threat

Journal

Biological psychiatry. Cognitive neuroscience and neuroimaging
ISSN: 2451-9030
Titre abrégé: Biol Psychiatry Cogn Neurosci Neuroimaging
Pays: United States
ID NLM: 101671285

Informations de publication

Date de publication:
11 2021
Historique:
received: 11 12 2020
revised: 21 03 2021
accepted: 12 04 2021
pubmed: 25 4 2021
medline: 19 11 2021
entrez: 24 4 2021
Statut: ppublish

Résumé

Overarching conceptualizations propose that the complex social-emotional effects of oxytocin (OXT) in humans are partly mediated by interactions with other neurotransmitter systems. Recent animal models suggest that the anxiolytic effects of OXT are critically mediated by the serotonin (5-HT) system, yet direct evidence in humans is lacking. To determine the role of 5-HT in OXT-induced attenuation of amygdala threat reactivity and sensitization/desensitization, we conducted a parallel-group, randomized, placebo-controlled, double-blind experiment during which 121 healthy subjects underwent a transient decrease in 5-HT signaling via acute tryptophan depletion or the corresponding placebo-control protocol before the administration of intranasal OXT or placebo intranasal spray, respectively. Mean and repetition-dependent changes in threat-specific amygdala reactivity toward threatening stimuli (angry faces) as assessed by functional magnetic resonance imaging served as the primary outcome. No main or interaction effects of treatment on amygdala threat reactivity were observed, yet OXT switched bilateral amygdala threat sensitization to desensitization, and this effect was significantly attenuated during decreased central 5-HT signaling via pretreatment with acute tryptophan depletion. The present findings provide the first evidence for a role of OXT in threat-specific amygdala desensitization in humans and suggest that these effects are critically mediated by the 5-HT system. OXT may have a therapeutic potential to facilitate amygdala desensitization, and adjunct upregulation of 5-HT neurotransmission may facilitate OXT's anxiolytic potential.

Sections du résumé

BACKGROUND
Overarching conceptualizations propose that the complex social-emotional effects of oxytocin (OXT) in humans are partly mediated by interactions with other neurotransmitter systems. Recent animal models suggest that the anxiolytic effects of OXT are critically mediated by the serotonin (5-HT) system, yet direct evidence in humans is lacking.
METHODS
To determine the role of 5-HT in OXT-induced attenuation of amygdala threat reactivity and sensitization/desensitization, we conducted a parallel-group, randomized, placebo-controlled, double-blind experiment during which 121 healthy subjects underwent a transient decrease in 5-HT signaling via acute tryptophan depletion or the corresponding placebo-control protocol before the administration of intranasal OXT or placebo intranasal spray, respectively. Mean and repetition-dependent changes in threat-specific amygdala reactivity toward threatening stimuli (angry faces) as assessed by functional magnetic resonance imaging served as the primary outcome.
RESULTS
No main or interaction effects of treatment on amygdala threat reactivity were observed, yet OXT switched bilateral amygdala threat sensitization to desensitization, and this effect was significantly attenuated during decreased central 5-HT signaling via pretreatment with acute tryptophan depletion.
CONCLUSIONS
The present findings provide the first evidence for a role of OXT in threat-specific amygdala desensitization in humans and suggest that these effects are critically mediated by the 5-HT system. OXT may have a therapeutic potential to facilitate amygdala desensitization, and adjunct upregulation of 5-HT neurotransmission may facilitate OXT's anxiolytic potential.

Identifiants

DOI: 10.1016/j.bpsc.2021.04.009 PMID: 33894423
pubmed: 33894423
pii: S2451-9022(21)00116-6
doi: 10.1016/j.bpsc.2021.04.009
pii:
doi:

Substances chimiques

Oxytocin 50-56-6

Types de publication

Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1081-1089

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Auteurs

Congcong Liu (C)

Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China.

Chunmei Lan (C)

Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China.

Keshuang Li (K)

School of Psychology and Cognitive Science, East China Normal University, Shanghai, China.

Feng Zhou (F)

Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China.

Shuxia Yao (S)

Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China.

Lei Xu (L)

Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China.

Ning Yang (N)

Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China.

Xinqi Zhou (X)

Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China.

Jiaxin Yang (J)

State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute of Brain Research, Beijing Normal University, Beijing, China.

Xue Yong (X)

State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute of Brain Research, Beijing Normal University, Beijing, China.

Yina Ma (Y)

State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute of Brain Research, Beijing Normal University, Beijing, China.

Dirk Scheele (D)

Division of Medical Psychology, Department of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, Germany; Department of Psychiatry, School of Medicine & Health Sciences, University of Oldenburg, Oldenburg, Germany.

Keith M Kendrick (KM)

Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China.

Benjamin Becker (B)

Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China. Electronic address: ben_becker@gmx.de.

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questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Voies d'administration de substances chimiques et des médicaments › Administration par voie topique › Administration par voie muqueuse › Administration par voie nasale › Oxytocinergic Modulation of Threat-Specific...
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questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Hormones peptidiques › Hormones hypophysaires › Hormones post-hypophysaires › Ocytocine › Oxytocinergic Modulation of Threat-Specific...