Cited by 132Neuroendocrine regulation and behaviorOlfactory and Sensory Function StudiesAdvanced Drug Delivery Systems

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Labeled oxytocin administered via the intranasal route reaches the brain in rhesus macaques

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Lee, M. R., Shnitko, T. A., Blue, S. W., Kaucher, A. V., Winchell, A. J., Erikson, D. W., Grant, K. A., Leggio, L.·2020·Nature Communications

DOI 10.1038/s41467-020-15942-1PMC PMC7270110

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Abstract

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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Fig. 1 Cerebrospinal fluid (CSF) d5 oxytocin (OT) concentrations: time course of d5OT concentrations in monkey cerebrospinal fluid (CSF) after intravenous (IV) administration of 80 and 40 IU d5OT (N = 6). No d5OT was detected after intranasal (IN) administration of 80 IU d5OT. Limit of quantification = 100 pg/ml.CC BY · PubMed Central

Fig. 2 Plasma d5 oxytocin (OT) concentrations: time course of d5OT concentrations in monkey plasma after intravenous (IV) and intranasal (IN) administration of 80 and 40 IU d5OT (N = 6). Limit of quantification = 100 pg/ml.CC BY · PubMed Central

Fig. 3 Cerebrospinal fluid (CSF) endogenous (d0) oxytocin (OT) concentrations: time course of d0OT in monkey cerebrospinal fluid (CSF) at baseline (Time = 0) and after intranasal (IN) d5OT 80 and 40 IU; after intravenous (IV) d5OT 80 and 40 IU. Limit of quantification = 10 pg/ml.CC BY · PubMed Central

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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.
ORCID: Lee, M. R.
Shnitko, T. A.
Kaucher, A. V.
Erikson, D. W.
Grant, K. A.
Leggio, L.
Venue: Nature Communications
Publisher: Springer Science and Business Media LLC
Published: 2020-06-03
Volume: 11
Issue: 1
Pages: 2783-2783
ISSN: 2041-1723 (ISSN-L)
DOI: 10.1038/s41467-020-15942-1
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
Licence: cc-by
creativecommons.org/licenses/by/4.0 (tdm)
creativecommons.org/licenses/by/4.0 (vor)
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: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › 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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Labeled oxytocin administered via the intranasal route reaches the brain in rhesus macaques

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