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Cited by 128Neuroendocrine regulation and behaviorNeuropeptides and Animal PhysiologyOlfactory and Sensory Function Studies

Plasma and CSF oxytocin levels after intranasal and intravenous oxytocin in awake macaques

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Freeman, Sara M., Samineni, Sridhar, Allen, Philip C., Stockinger, Diane, Bales, Karen L., Hwa, Granger G.C., Roberts, Jeffrey A.·2016·Psychoneuroendocrinology
DOI 10.1016/j.psyneuen.2016.01.014
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Abstract

Oxytocin (OT) is a neuropeptide that mediates a variety of complex social behaviors in animals and humans. Intranasal OT has been used as an experimental therapeutic for human conditions characterized by deficits in social functioning, especially autism spectrum disorder and schizophrenia. However, it is currently under intense debate whether intranasal delivery of OT reaches the central nervous system. In this study, four female rhesus macaques were implanted with chronic intrathecal catheters and used to investigate the pharmacokinetic profile of OT in the central nervous system and the peripheral vasculature following intravenous (IV) and intranasal (IN) administration of OT. In a randomized, crossover design, OT was given to four awake monkeys at three different doses based on body weight (0.1 IU/kg; 1 IU/kg; 5 IU/kg). A time course of concurrent cerebrospinal fluid (CSF) and plasma samples were taken following administration. We found a dose-dependent effect of IV OT treatment on plasma OT levels, which peaked at 5 min post-dose and gradually returned to baseline by 120 min. In contrast, a change in CSF OT was only observed at the highest IV dose (5 IU/kg) at 15 min post-dose and gradually returned to baseline by 120 min. After IN administration, there was no significant change in plasma OT at any of the three doses. However, at the highest dose level, we found a significant increase in CSF OT at 15-30 min post- dose. The results of this study in light of recent, similar publications highlight the importance of methodological consistency across studies. This study also establishes a non-human primate model that can provide a stable platform for carrying out serial sampling from the central nervous system and peripheral vasculature concurrently.

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  • Recent findings have demonstrated that intranasal oxytocin increases oxytocin concentration in cerebrospinal fluid in both humans and animals.

    “Recent findings have demonstrated that IN-OT increases OT concentration in CSF in both human (25) and animal (38,39).”

    From Is there a Publication Bias in Behavioural Intranasal Oxytocin Research on Humans? Opening the File Drawer of One Laboratory (2016) · cites this paper as [39]

  • In monkeys, a small dose of intranasal oxytocin between 0.58 and 5.5 IU did not increase cerebrospinal fluid oxytocin, while a larger dose between 29 and 36.5 IU increased cerebrospinal fluid oxytocin 15 to 30 minutes after spray intake.

    “Authors reported that while a small dose of IN-OT (between 0.58 and 5.5 IU) did not increase CSF OT, a bigger dose that is frequently used in human trials (between 29 and 36.5 IU) increases CSF OT 15–30 min following spray intake (Freeman et al. 2016).”

    From A precision medicine approach to oxytocin trials (2017) · cites this paper as Freeman et al. 2016

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Authors
Freeman, S. M., Samineni, S., Allen, P. C., Stockinger, D., Bales, K. L., Hwa, G. G. C., & Roberts, J. A.
Affiliations
University of California, Davis (US)
Corresponding author
Hwa, Granger G.C.
ORCID
Venue
Psychoneuroendocrinology
Publisher
Elsevier BV
Published
2016-04
Volume
66
Pages
185-194
ISSN
0306-4530 (ISSN-L)
DOI
10.1016/j.psyneuen.2016.01.014
OpenAlex
W2273251030
Cited by
128
References
40
Citations by year
2026: 5 · 2025: 6 · 2024: 7 · 2023: 5 · 2022: 7 · 2021: 20 · 2020: 7 · 2019: 15 · 2018: 16 · 2017: 27 · 2016: 13
FWCI
37.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Psychoneuroendocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
Topics
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
Keywords
oxytocin, intranasal administration, intravenous administration, cerebrospinal fluid, plasma oxytocin, pharmacokinetics, rhesus monkeys, central nervous system delivery, dose-dependent effects, nonhuman primate model, social behavior
MeSH terms
Administration, Intranasal, Animals, Behavior, Animal, Central Nervous System, Female, Macaca mulatta, Oxytocin, Random Allocation, Social Behavior, Wakefulness, Cross-Over Studies, Infusions, Intraventricular, Administration, Intravenous

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