Switching brain serotonin with oxytocin
Open accessAbstract
Serotonin (5-HT) and oxytocin (OXT) are two neuromodulators involved in human affect and sociality and in disorders like depression and autism. We asked whether these chemical messengers interact in the regulation of emotion-based behavior by administering OXT or placebo to 24 healthy subjects and mapping cerebral 5-HT system by using 2'-methoxyphenyl-(N-2'-pyridinyl)-p-[(18)F]fluoro-benzamidoethylpiperazine ([(18)F]MPPF), an antagonist of 5-HT1A receptors. OXT increased [(18)F]MPPF nondisplaceable binding potential (BPND) in the dorsal raphe nucleus (DRN), the core area of 5-HT synthesis, and in the amygdala/hippocampal complex, insula, and orbitofrontal cortex. Importantly, the amygdala appears central in the regulation of 5-HT by OXT: [(18)F]MPPF BPND changes in the DRN correlated with changes in right amygdala, which were in turn correlated with changes in hippocampus, insula, subgenual, and orbitofrontal cortex, a circuit implicated in the control of stress, mood, and social behaviors. OXT administration is known to inhibit amygdala activity and results in a decrease of anxiety, whereas high amygdala activity and 5-HT dysregulation have been associated with increased anxiety. The present study reveals a previously unidentified form of interaction between these two systems in the human brain, i.e., the role of OXT in the inhibitory regulation of 5-HT signaling, which could lead to novel therapeutic strategies for mental disorders.
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Oxytocin administration modulates serotonin (5-HT) synthesis and 5-HT receptor binding potential, resulting in an overall modulation of the serotonergic system.
“Previous data have also demonstrated that oxytocin administration modulates serotonin (5-HT) synthesis and 5-HT receptor binding potential, resulting in an overall modulation of the serotonergic system (Mottolese et al., 2014).”
From The oxytocin receptor represents a key hub in the GPCR heteroreceptor network: Potential relevance for brain and behavior (2022) · cites this paper as Mottolese et al., 2014
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Sleep Medicine - Asleep or Awake?
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- Authors
- Mottolese, R., Redouté, J., Costes, N., Le Bars, D., & Sirigu, A.
- Affiliations
- Center for Cognitive Neuroscience, Unité Mixte de Recherche 5229, Centre National de la Recherche Scientifique, 69675 Bron, France;
- Lyon 1 Université (FR)
- Centre d'Etude et de Recherche Multimodal et Pluridisciplinaire Imagerie du Vivant, 69003 Lyon, France
- University Claude Bernard Lyon 1, 69609 Lyon, France; and
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-05-27
- Volume
- 111
- Issue
- 23
- Pages
- 8637-8642
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4060712
- OpenAlex
- W2033720614
- Cited by
- 179
- References
- 58
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 10 · 2023: 13 · 2022: 16 · 2021: 18 · 2020: 16 · 2019: 12 · 2018: 14 · 2017: 22 · 2016: 13 · 2015: 18 · 2014: 3
- FWCI
- 27.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- serotonin, oxytocin, 5-HT1A receptor, dorsal raphe nucleus, amygdala, hippocampus, insula, orbitofrontal cortex, anxiety, social behavior, depression, autism spectrum disorder
- MeSH terms
- Administration, Intranasal, Adult, Amygdala, Binding, Competitive, Brain, Double-Blind Method, Frontal Lobe, Gyrus Cinguli, Hippocampus, Humans, Male, Oxytocin, Piperazines, Pyridines, Raphe Nuclei, Serotonin, Signal Transduction, Receptor, Serotonin, 5-HT1A, Positron-Emission Tomography, Young Adult, Serotonin 5-HT1 Receptor Antagonists
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