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

M. R. Lee; T. A. Shnitko; S. W. Blue; A. V. Kaucher; A. J. Winchell; D. W. Erikson; K. A. Grant; L. Leggio

doi:10.1038/s41467-020-15942-1

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

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

Oregon National Primate Research Center

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

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.

Original language	English (US)
Article number	2783
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-15942-1
State	Published - Dec 1 2020

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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title = "Labeled oxytocin administered via the intranasal route reaches the brain in rhesus macaques",

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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note = "Funding Information: This work was supported by (1) National Institutes of Health (NIH) intramural funding ZIA-AA000218 (Section on Clinical Psychoneuroendocrinology and Neuropsycho-pharmacology; PI: L.L.), jointly supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) Division of Intramural Clinical and Biological Research and the National Institute on Drug Abuse (NIDA) Intramural Research Program (IRP); (2) NIH NIAAA R24 AA019431 grant (PI: K.A.G.); and (3) NIH Office of the Director P51 OD011092 grant (PI: Dr. P. Barr-Gielspe) Publisher Copyright: {\textcopyright} 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

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doi = "10.1038/s41467-020-15942-1",

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AU - Grant, K. A.

AU - Leggio, L.

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N2 - 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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Labeled oxytocin administered via the intranasal route reaches the brain in rhesus macaques

Abstract

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