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Study · Randomized controlled trial · n = 112 · 2022

3 results

Oxytocinergic Modulation of Stress-Associated Amygdala-Hippocampus Pathways in Humans Is Mediated by Serotonergic Mechanisms.

Lan C, Liu C, Li K, Zhao Z, Yang J, Ma Y, Scheele D, Yao S, Kendrick KM, Becker B

The international journal of neuropsychopharmacology1 Oct 2022Cited by 17 (Europe PMC)

Summary

BackgroundThe hypothalamic neuropeptide oxytocin (OXT) may exert anxiolytic and stress-reducing actions via modulatory effects on amygdala circuits. Animal models and initial findings in humans suggest that some of these effects are mediated by interactions with other neurotransmitter systems, in particular the serotonin (5-HT) system. Against this background, the present pharmacological resting-state functional magnetic resonance imaging study aimed to determine whether effects of OXT on stress-associated amygdala intrinsic networks are mediated by 5-HT.MethodsWe employed a randomized, placebo-controlled, double-blind parallel-group, pharmacological functional magnetic resonance imaging resting-state experiment with 4 treatment groups in n = 112 healthy male participants. Participants underwent a transient decrease in 5-HT signaling via acute tryptophan depletion (ATD) or a corresponding placebo-control protocol before the administration of intranasal OXT (24 IU) or placebo intranasal spray.ResultsOXT and 5-HT modulation exerted interactive effects on the coupling of the left amygdala with the ipsilateral hippocampus and adjacent midbrain. OXT increased intrinsic coupling in this pathway, whereas this effect of OXT was significantly attenuated during transiently decreased central serotonergic signaling induced via acute tryptophan depletion. In the absence of OXT or 5-HT modulation, this pathway showed a trend for an association with self-reported stress perception in everyday life. No interactive effects were observed for the right amygdala.ConclusionsTogether, the findings provide the first evidence, to our knowledge, that the effects of OXT on stress-associated amygdala-hippocampal-midbrain pathways are critically mediated by the 5-HT system in humans.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

3 results from studies that gave the peptide. 3 results from people.

  1. 01HumanRandomized controlled trialMechanism

    In healthy men, intranasal oxytocin increased intrinsic coupling of the left amygdala with the ipsilateral hippocampus and adjacent midbrain.

    In plain wordsIn healthy men, oxytocin spray increased the connection between the left amygdala and the hippocampus and midbrain areas.

    Peptide
    Oxytocin
    Outcome
    IncreaseLeft amygdala to ipsilateral hippocampus and midbrain coupling
    Study

    n = 112

    Comparator
    Placebo
    Outcome group
    Brain and neuronal activity · Nervous system and cognition
    Studied dose
    24 IU · intranasalAs given in this study (human).

    Source sentences

    Summary
    OXT increased intrinsic coupling in this pathway
    2 context sentences
    Summary · context
    We employed a randomized, placebo-controlled, double-blind parallel-group, pharmacological functional magnetic resonance imaging resting-state experiment with 4 treatment groups in n = 112 healthy male participants.
    Summary · context
    Participants underwent a transient decrease in 5-HT signaling via acute tryptophan depletion (ATD) or a corresponding placebo-control protocol before the administration of intranasal OXT (24 IU) or placebo intranasal spray.
  2. 02HumanRandomized controlled trialMechanism

    In healthy men, the oxytocin-induced increase in left amygdala-hippocampus coupling was significantly attenuated during lowered serotonin signaling.

    In plain wordsIn healthy men, the effect of oxytocin on this brain connection was weaker when serotonin signaling was lowered.

    Peptide
    Oxytocin
    Outcome
    DecreaseOxytocin effect on amygdala-hippocampus coupling during acute tryptophan depletion
    Study

    n = 112

    Comparator
    Oxytocin without tryptophan depletion
    Outcome group
    Brain and neuronal activity · Nervous system and cognition
    Studied dose
    24 IU · intranasalAs given in this study (human).

    Source sentences

    Summary
    whereas this effect of OXT was significantly attenuated during transiently decreased central serotonergic signaling induced via acute tryptophan depletion.
    3 context sentences
    Summary · context
    OXT and 5-HT modulation exerted interactive effects on the coupling of the left amygdala with the ipsilateral hippocampus and adjacent midbrain.
    Summary · context
    We employed a randomized, placebo-controlled, double-blind parallel-group, pharmacological functional magnetic resonance imaging resting-state experiment with 4 treatment groups in n = 112 healthy male participants.
    Summary · context
    Participants underwent a transient decrease in 5-HT signaling via acute tryptophan depletion (ATD) or a corresponding placebo-control protocol before the administration of intranasal OXT (24 IU) or placebo intranasal spray.
  3. 03HumanRandomized controlled trialMechanism

    In healthy men, no interactive effects of oxytocin and serotonin modulation were observed for the right amygdala.

    In plain wordsIn healthy men, oxytocin and lowered serotonin signaling did not interact on the right amygdala.

    Peptide
    Oxytocin
    Outcome
    No significant changeRight amygdala coupling, oxytocin by serotonin interaction
    Study

    n = 112

    Comparator
    Placebo
    Outcome group
    Brain and neuronal activity · Nervous system and cognition
    Studied dose
    24 IU · intranasalAs given in this study (human).

    Source sentences

    Summary
    No interactive effects were observed for the right amygdala.
    2 context sentences
    Summary · context
    We employed a randomized, placebo-controlled, double-blind parallel-group, pharmacological functional magnetic resonance imaging resting-state experiment with 4 treatment groups in n = 112 healthy male participants.
    Summary · context
    Participants underwent a transient decrease in 5-HT signaling via acute tryptophan depletion (ATD) or a corresponding placebo-control protocol before the administration of intranasal OXT (24 IU) or placebo intranasal spray.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    11 Oct 2026, 00:50 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 02:49 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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