Intranasal administration of oxytocin: behavioral and clinical effects, a review
Open accessAbstract
The intranasal (IN-) administration of substances is attracting attention from scientists as well as pharmaceutical companies. The effects are surprisingly fast and specific. The present review explores our current knowledge about the routes of access to the cranial cavity. 'Direct-access-pathways' from the nasal cavity have been described but many additional experiments are needed to answer a variety of open questions regarding anatomy and physiology. Among the IN-applied substances oxytocin (OT) has an extensive history. Originally applied in women for its physiological effects related to lactation and parturition, over the last decade most studies focused on their behavioral 'prosocial' effects: from social relations and 'trust' to treatment of 'autism'. Only very recently in a microdialysis study in rats and mice, the 'direct-nose-brain-pathways' of IN-OT have been investigated directly, implying that we are strongly dependent on results obtained from other IN-applied substances. Especially the possibility that IN-OT activates the 'intrinsic' OT-system in the hypothalamus as well needs further clarification. We conclude that IN-OT administration may be a promising approach to influence human communication but that the existing lack of information about the neural and physiological mechanisms involved is a serious problem for the proper understanding and interpretation of the observed effects.
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A positive feedback system between peripheral and central oxytocin concentrations controls the duration of elevated peripheral oxytocin.
“Together, these results support the idea of a positive feedback system between peripheral and central concentrations of OT: “… central regulating mechanisms [control] the duration of the elevated levels of peripheral OT” [[1] p. 1450].”
From Salivary oxytocin concentrations in males following intranasal administration of oxytocin: a double-blind, cross-over study (2015) · cites this paper as [1]
There is a lack of evidence concerning both the longevity of intranasal oxytocin effects on peripheral oxytocin concentrations and the pattern of concentrations during these effects.
“In particular, there is a lack of evidence concerning both the longevity of the effects of intranasal spray on peripheral OT concentrations and the pattern of concentrations during these effects [1].”
From Salivary oxytocin concentrations in males following intranasal administration of oxytocin: a double-blind, cross-over study (2015) · cites this paper as [1]
Few studies have addressed the longevity and pattern of salivary oxytocin after intranasal oxytocin, and many intranasal oxytocin administration studies do not include any assessment of participants' oxytocin concentrations.
“Few studies have addressed these questions, and many IN-OT administration studies do not include any assessment of participants’ OT concentrations.”
From Salivary oxytocin concentrations in males following intranasal administration of oxytocin: a double-blind, cross-over study (2015) · cites this paper as [1]
Oxytocin concentrations may peak earlier than 30 minutes, as is the case for many other small peptides.
“It is nonetheless worth noting that concentrations may peak earlier than 30 minutes, as is the case for many other small peptides [1], and can be reliably measured in other matrices.”
From Salivary oxytocin concentrations in males following intranasal administration of oxytocin: a double-blind, cross-over study (2015) · cites this paper as [1]
Central effects are observed in humans after intranasal administration of OXT/AVP.
“Whatever the mechanism(s) involved, there is no doubt that central effects are observed in humans after intranasal administration (Veening and Olivier, 2013).”
From Chronic and acute intranasal oxytocin produce divergent social effects in mice (2014) · cites this paper as Veening and Olivier, 2013
The delay of only 5 min was chosen based on evidence indicating that intranasal administration of OXT has very rapid pharmacokinetics with effects expected to appear already within a few minutes.
“The delay of only 5 min was chosen based on evidence indicating that intranasal administration of OXT has very rapid pharmacokinetics with effects expected to appear already within a few minutes (Veening and Olivier, 2013).”
From Chronic and acute intranasal oxytocin produce divergent social effects in mice (2014) · cites this paper as Veening and Olivier, 2013
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References 485 · Cited by 169
Research works printed but not linked: 2
- Dhuria S.V. Hanson L.R. Frey W.H. 2nd Intranasal delivery to the central nervous system: mechanisms and experimental considerations J. Pharm. Sci. 99 2010 1654 1673 19877171
- Shipley M.T. Ennis M. Puche A. Olfactory system Paxinos G. The Rat Nervous System third ed. 2004 Elsevier San Diego 922 963
- Authors
- Veening, J. G., & Olivier, B.
- Affiliations
- Radboud University Nijmegen (NL)
- Utrecht University (NL)
- Corresponding author
- Veening, Jan G.
- ORCID
- Olivier, Berend
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 37
- Issue
- 8
- Pages
- 1445-1465
- ISSN
- 0149-7634 (ISSN-L)
- PMC
- PMC7112651
- OpenAlex
- W2144745726
- Cited by
- 169
- References
- 485
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 8 · 2023: 7 · 2022: 7 · 2021: 20 · 2020: 9 · 2019: 11 · 2018: 16 · 2017: 16 · 2016: 19 · 2015: 18 · 2014: 17 · 2013: 10
- FWCI
- 2.83
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Topics
- Social Sciences › Psychology › Social Psychology › 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
- intranasal administration, oxytocin, nasal cavity, prosocial behavior, trust, autism treatment, interpersonal relationships, microdialysis, human communication
- MeSH terms
- Administration, Intranasal, Animals, Behavior, Animal, Brain, Humans, Neurons, Oxytocin, Social Behavior, Mice, Rats
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