Oxytocin by intranasal and intravenous routes reaches the cerebrospinal fluid in rhesus macaques: determination using a novel oxytocin assay
Open accessAbstract
Oxytocin (OT) is a potential treatment for multiple neuropsychiatric disorders. As OT is a peptide, delivery by the intranasal (IN) route is the preferred method in clinical studies. Although studies have shown increased cerebrospinal fluid (CSF) OT levels following IN administration, this does not unequivocably demonstrate that the peripherally administered OT is entering the CSF. For example, it has been suggested that peripheral delivery of OT could lead to central release of endogenous OT. It is also unknown whether the IN route provides for more efficient entry of the peptide into the CSF compared to the intravenous (IV) route, which requires blood-brain barrier penetration. To address these questions, we developed a sensitive and specific quantitative mass spectrometry assay that distinguishes labeled (d5-deuterated) from endogenous (d0) OT. We administered d5 OT (80 IU) to six nonhuman primates via IN and IV routes as well as IN saline as a control condition. We measured plasma and CSF concentrations of administered and endogenous OT before (t=0) and after (t=10, 20, 30, 45 and 60 min) d5 OT dosing. We demonstrate CSF penetrance of d5, exogenous OT delivered by IN and IV administration. Peripheral administration of d5 OT did not lead to increased d0, endogenous OT in the CSF. This suggests that peripheral administration of OT does not lead to central release of endogenous OT. We also did not find that IN administration offered an advantage compared to IV administration with respect to achieving greater CSF concentrations of OT.
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Intranasal oxytocin elevates brain-level presence of oxytocin.
“intranasal oxytocin elevates brain-level presence of oxytocin”
From Oxytocin promotes coordinated out-group attack during intergroup conflict in humans (2019) · cites this paper as Lee et al., 2018
Exogenous oxytocin is administered intranasally to humans because this is likely the most efficient route for oxytocin to penetrate the brain and bypass the blood-brain barrier.
“Exogenously, oxytocin is administered intranasally (IN-OT) to humans given that this is likely the most efficient route for OT to penetrate the brain and bypass the blood–brain barrier (BBB) (Lee et al. 2017).”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Lee et al. 2017
A mass spectrometry study found a significant cerebrospinal fluid increase in labeled oxytocin solely related to exogenous intranasal oxytocin delivery.
“Authors found that a significant CSF increase in labeled OT that is solely related to the exogenous IN-OT delivery (Lee et al. 2017).”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Lee et al. 2017
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“They concluded that IN treatment of OT does not lead to central release of endogenous OT, instead the administered deuterated-OT penetrates into the CSF (Lee et al., 2018) crossing the blood-brain barrier via a yet unknown mechanism.”
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- Authors
- Lee, M. R., Scheidweiler, K. B., Diao, X. X., Akhlaghi, F., Cummins, A., Huestis, M. A., Leggio, L., & Averbeck, B. B.
- Affiliations
- National Institutes of Health (US)
- University of Rhode Island (US)
- Corresponding author
- Lee, M R
- Venue
- Molecular Psychiatry
- Published
- 2017-03-14
- Volume
- 23
- Issue
- 1
- Pages
- 115-122
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC5862033
- OpenAlex
- W2724271447
- Cited by
- 235
- References
- 30
- Citations by year
- 2026: 3 · 2025: 13 · 2024: 15 · 2023: 15 · 2022: 16 · 2021: 46 · 2020: 38 · 2019: 34 · 2018: 36 · 2017: 18
- FWCI
- 49.07
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Journal of Media Literacy Education (submittedVersion, cc-by)
- Digital Commons - URI (University of Rhode Island) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (UH2TR000963)
- National Institute of Mental Health (ZIAMH002928)
- National Center for Advancing Translational Sciences
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- oxytocin, intranasal administration, intravenous administration, cerebrospinal fluid, CSF penetration, blood-brain barrier, endogenous oxytocin, mass spectrometry assay, rhesus monkeys, non-human primates, peptide delivery
- MeSH terms
- Correlation of Data, Administration, Intranasal, Animals, Chromatography, High Pressure Liquid, Macaca mulatta, Male, Oxytocin, Time Factors, Area Under Curve, Administration, Intravenous
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