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Aerosolized oxytocin increases cerebrospinal fluid oxytocin in rhesus macaques
Open accessAbstract
Intranasal (IN) administration is a widely used method for examining the effect of oxytocin (OT) on social behavior and cognition in healthy subjects and psychiatric populations. IN-OT in humans enhances trust, emotional perception, and empathetic behavior and is under investigation as a potential pharmacotherapy to enhance social functioning in a variety of neuropsychiatric disorders, including autism spectrum disorders (ASD). Nonhuman primates (NHP) are an important model for understanding the effect of OT on social cognition, its neural mechanisms, and the development of IN-OT as a pharmacotherapy for treating social deficits in humans. However, NHP and even some human populations, such as very young infants and children, cannot easily follow the detailed self-administration protocol used in the majority of human IN-OT studies. Therefore, we evaluated the efficacy of several OT-administration routes for elevating central OT concentrations in rhesus macaques. First, we examined the effect of IN and intravenous (IV) routes of OT administration on concentrations of OT and vasopressin (AVP) in plasma and lumbar CSF. Second, we examined these same measures in monkeys after an aerosolized (AE) OT delivery route. All three administration routes significantly increased plasma OT concentrations, but only the AE-OT route significantly increased concentrations of CSF OT. No route affected concentrations of AVP in plasma or CSF. This study confirms that the AE route is the most effective method for increasing central OT concentrations in monkeys, and may also be an effective route, alternative to IN, for administering OT to some human populations.
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In the citing paper
“In a larger study, Modi et al. gave 24IU oxytocin (~5µg/kg body weight) to macaques by spray or aerosol; only the aerosol produced a significant increase in CSF (from ~20 to ~60pg/ml) (25).”
From Intranasal Oxytocin: Myths and Delusions (2016) · cites this paper as [25]
Experimental — accuracy not yet measuredIn the citing paper
“The intranasal dose administered in the present study has been associated with changes in central function in humans 58, and similar or smaller doses of oxytocin or vasopressin (24–48 IU for oxytocin; 40–80 IU for vasopressin) have been associated with elevations in peptide levels in the cerebrospinnal fluid in humans or macaques of no more than approximately 55 pg/ml in actual levels 70, 71, 72,”
From The Analgesic Effect of Oxytocin in Humans: A Double‐Blind, Placebo‐Controlled Cross‐Over Study Using Laser‐Evoked Potentials (2016) · cites this paper as [72]
In the citing paper
“In addition, several studies have found that IN-OT leads to a significant increase in OT concentrations in cerebrospinal fluid, which may also be indicative of IN-OT reaching the brain [30, 31].”
From Salivary oxytocin concentrations in males following intranasal administration of oxytocin: a double-blind, cross-over study (2015) · cites this paper as [31]
In the citing paper
“Also, in monkeys, IN-OT or OT intake via a nebulizer (25 or 48 IU) increased OT CSF concentration compared to placebo (Chang et al. 2012; Dal Monte et al. 2014; Modi et al. 2014).”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Modi et al. 2014
In the citing paper
“While there is conflicting evidence on whether peripheral OT can cross the BBB (Modi et al., 2014), our study suggests that even if OT does travel across this barrier in small amounts, this quantity is not large enough to dampen amygdala activity compared to placebo.”
From Low dose intranasal oxytocin delivered with Breath Powered device dampens amygdala response to emotional stimuli: A peripheral effect-controlled within-subjects randomized dose-response fMRI trial (2016) · cites this paper as Modi et al., 2014
In the citing paper
“The here-observed immediate influence of intranasal oxytocin on psychopathology and hence on brain function is supported by primate studies showing that intranasal oxytocin, such as other intranasally administered anxiolytic neuropeptides like NPS [45], are able to reach the cerebrospinal fluid [46, 47] and thus, assumingly, also the brain.”
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Citations
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Metadata
- Authors
- Modi, M. E., Connor-Stroud, F., Landgraf, R., Young, L. J., & Parr, L. A.
- Affiliations
- Emory University (US)
- Max Planck Institute of Psychiatry (DE)
- Corresponding author
- Modi, Meera E.
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 45
- Pages
- 49-57
- ISSN
- 0306-4530 (ISSN-L)
- PMC
- PMC4120060
- OpenAlex
- W2043628043
- Cited by
- 129
- References
- 53
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 7 · 2019: 16 · 2018: 23 · 2017: 18 · 2016: 24 · 2015: 15 · 2014: 9
- FWCI
- 32.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- National Science Foundation
- Emory University
- National Institutes of Health (P51OD011132)
- Yerkes National Primate Research Center, Emory University
- National Institute of Mental Health (K02MH064692, MH064692, MH068791, R21MH090776, R01MH068791, P50MH100023)
- National Center for Research Resources (P51RR165, P51RR000165)
- Office of Research Infrastructure Programs, National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- oxytocin, rhesus monkeys, intranasal administration, intravenous administration, vasopressin, route of administration, social cognition, autism spectrum disorder, pharmacotherapy
- MeSH terms
- Administration, Intranasal, Aerosols, Animals, Biological Availability, Macaca mulatta, Male, Oxytocin, Time Factors, Up-Regulation, Nasal Sprays, Administration, Intravenous
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