Labeled oxytocin administered via the intranasal route reaches the brain in rhesus macaques
Open accessAbstract
Oxytocin may have promise as a treatment for neuropsychiatric disorders. Its therapeutic effect may depend on its ability to enter the brain and bind to the oxytocin receptor. To date, the brain tissue penetrance of intranasal oxytocin has not been demonstrated. In this nonhuman primate study, we administer deuterated oxytocin intranasally and intravenously to rhesus macaques and measure, with mass spectrometry, concentrations of labeled (exogenously administered) and endogenous oxytocin in 12 brain regions two hours after oxytocin administration. Labeled oxytocin is quantified after intranasal (not intravenous) administration in brain regions (orbitofrontal cortex, striatum, brainstem, and thalamus) that lie in the trajectories of the olfactory and trigeminal nerves. These results suggest that intranasal administration bypasses the blood–brain barrier, delivering oxytocin to specific brain regions, such as the striatum, where oxytocin acts to impact motivated behaviors. Further, high concentrations of endogenous oxytocin are in regions that overlap with projection fields of oxytocinergic neurons.
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There is uncertainty regarding absorption, brain penetration, and time course of effects with intranasal oxytocin.
“There is uncertainty regarding absorption, brain penetration, and time course of effects with intranasal oxytocin35,36 that may be amplified by differences among specific preparations of intranasal oxytocin.”
From Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder (2021) · cites this paper as [35]
The Discussion (page not provided) says the extent and regional distribution of brain penetration need further study and that the two-hour sampling interval limits what can be inferred about timing. But the paper demonstrates brain penetration in rhesus macaques; it does not directly assess the time course of oxytocin’s effects or establish uncertainty about absorption. The claim is therefore supported only in part. (LLM, conf=0.85)
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- Authors
- Lee, M. R., Shnitko, T. A., Blue, S. W., Kaucher, A. V., Winchell, A. J., Erikson, D. W., Grant, K. A., & Leggio, L.
- Affiliations
- National Institutes of Health (US)
- Oregon National Primate Research Center (US)
- Corresponding author
- Lee, M. R.
- Venue
- Nature Communications
- Published
- 2020-06-03
- Volume
- 11
- Issue
- 1
- Pages
- 2783-2783
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7270110
- OpenAlex
- W3031412498
- Cited by
- 132
- References
- 44
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 15 · 2023: 19 · 2022: 27 · 2021: 34 · 2020: 13
- FWCI
- 25.40
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (OD-011092, P51OD011092)
- National Institute on Alcohol Abuse and Alcoholism (ZIAAA000218, AA 019431, AA000218, R03AA028071, R24AA019431)
- National Institute on Drug Abuse (ZIA-AA000218, AA000218)
- NIH Office of the Director (P51 OD011092, OD011092)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- oxytocin, intranasal administration, brain penetration, rhesus monkeys, blood-brain barrier bypass, olfactory pathway, trigeminal pathway, striatum, orbitofrontal cortex, thalamus, brainstem, endogenous oxytocin, oxytocin receptor, motivated behavior, neuropsychiatric disorders
- MeSH terms
- Administration, Intranasal, Animals, Brain, Dose-Response Relationship, Drug, Female, Macaca mulatta, Male, Oxytocin, Staining and Labeling, Limit of Detection
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