Kinetics and dose dependency of intranasal oxytocin effects on amygdala reactivity
Abstract
Background Current neuroimaging perspectives on a variety of mental disorders emphasize dysfunction of the amygdala. The neuropeptide oxytocin (OXT), a key mediator in the regulation of social cognition and behavior, accumulates in cerebrospinal fluid after intranasal administration in macaques and humans and modulates amygdala reactivity in both species. However, the translation of neuromodulatory OXT effects to novel treatment approaches is hampered by the absence of studies defining the most effective dose and dose-response latency for targeting the amygdala.Methods To address this highly relevant issue, a total of 116 healthy men underwent functional magnetic resonance imaging using a randomized, double-blind, placebo-controlled crossover study design. The experimental rationale was to systematically vary dose-test latencies (15-40, 45-70, and 75-100 minutes) and doses of OXT (12, 24, and 48 international units) in order to identify the most robust effects on amygdala reactivity. During functional magnetic resonance imaging, subjects completed an emotional face recognition task including stimuli with varying intensities ranging from low (highly ambiguous) to high (less ambiguous).Results Our results indicate that the OXT-induced inhibition of amygdala responses to fear was most effective in a time window between 45 and 70 minutes after administration of a dose of 24 international units. Furthermore, the observed effect was most evident in subjects scoring high on measures of autistic-like traits. Behavioral response patterns suggest that OXT specifically reduced an emotional bias in the perception of ambiguous faces.Conclusions These findings provide initial evidence of the most effective dose and dose-test interval for future experimental or therapeutic regimens aimed at targeting amygdala functioning using intranasal OXT administration.
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A 24 IU dosage has been shown as having more pronounced effects (compared with 12 or 48 IU dose of oxytocin) on behavioral and neural responses.
“recently shown as having more pronounced effects (compared with 12 or 48 IU dose of oxytocin) on behavioral and neural responses (Spengler et al., 2017).”
From Oxytocin promotes coordinated out-group attack during intergroup conflict in humans (2019) · cites this paper as Spengler et al., 2017
A previous study revealed a dose-dependent effect of OT (12, 24, and 48 IU), with the 24-IU dose being most effective in inhibiting amygdala activity during negative emotional processing.
“A previous study has revealed a dose-dependent effect of OT (12, 24, and 48 IU), with the 24-IU dose being most effective in inhibiting amygdala activity during negative emotional processing (Spengler et al., 2017).”
From Oxytocin facilitates approach behavior to positive social stimuli via decreasing anterior insula activity (2018) · cites this paper as Spengler et al., 2017
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A registered replication study on oxytocin and trust
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- Authors
- Spengler, F. B., Schultz, J., Scheele, D., Essel, M., Maier, W., Heinrichs, M., & Hurlemann, R.
- Affiliations
- University of Bonn (DE)
- University of Freiburg (DE)
- Corresponding author
- Hurlemann, René
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2017-12
- Volume
- 82
- Issue
- 12
- Pages
- 885-894
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2613162307
- Semantic Scholar
- 839068409dc840622268e4558d0a316e5e66f93c
- Cited by
- 229
- References
- 96
- Citations by year
- 2026: 15 · 2025: 16 · 2024: 22 · 2023: 23 · 2022: 21 · 2021: 37 · 2020: 34 · 2019: 32 · 2018: 22 · 2017: 6
- FWCI
- 36.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Research Bank (Australian Catholic University) (submittedVersion)
- DZNE Pub (submittedVersion)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Face Recognition and Perception
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- intranasal oxytocin, amygdala reactivity, dose-response relationship, fear conditioning, facial emotion recognition, autistic traits, social cognition, neuromodulation
- MeSH terms
- Facial Recognition, Administration, Intranasal, Adult, Amygdala, Brain Mapping, Dose-Response Relationship, Drug, Double-Blind Method, Emotions, Humans, Kinetics, Magnetic Resonance Imaging, Male, Oxytocin, Psychotropic Drugs, Time Factors, Cross-Over Studies, Young Adult
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