Nasal oxytocin administration reduces food intake without affecting locomotor activity and glycemia with c-Fos induction in limited brain areas
Abstract
Recent studies have considered oxytocin (Oxt) as a possible medicine to treat obesity and hyperphagia. To find the effective and safe route for Oxt treatment, we compared the effects of its nasal and intraperitoneal (IP) administration on food intake, locomotor activity, and glucose tolerance in mice. Nasal Oxt administration decreased food intake without altering locomotor activity and increased the number of c-Fos-immunoreactive (ir) neurons in the paraventricular nucleus (PVN) of the hypothalamus, the area postrema (AP), and the dorsal motor nucleus of vagus (DMNV) of the medulla. IP Oxt administration decreased food intake and locomotor activity and increased the number of c-Fos-ir neurons not only in the PVN, AP, and DMNV but also in the nucleus of solitary tract of the medulla and in the arcuate nucleus of the hypothalamus. In IP glucose tolerance tests, IP Oxt injection attenuated the rise of blood glucose, whereas neither nasal nor intracerebroventricular Oxt affected blood glucose. In isolated islets, Oxt administration potentiated glucose-induced insulin secretion. These results indicate that both nasal and IP Oxt injections reduce food intake to a similar extent and increase the number of c-Fos-ir neurons in common brain regions. IP Oxt administration, in addition, activates broader brain regions, reduces locomotor activity, and affects glucose tolerance possibly by promoting insulin secretion from pancreatic islets. In comparison with IP administration, the nasal route of Oxt administration could exert a similar anorexigenic effect with a lesser effect on peripheral organs.
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Maejima et al. reported that 10 μg intranasal oxytocin activated Fos expression in the paraventricular nucleus, area postrema, and dorsal motor nucleus of the vagus; the area postrema lies outside the blood-brain barrier and should not be reachable from CSF, and the same areas were activated by systemic oxytocin.
“Maejima et al. reported that intranasal administration of a higher dose of oxytocin (10µg) activated Fos expression at the paraventricular nucleus, the area postrema and the dorsal motor nucleus of the vagus (29).The area postrema is outside the blood-brain barrier, and should not be accessible to oxytocin from the CSF.These same areas were also activated by oxytocin given systemically.”
From Intranasal Oxytocin: Myths and Delusions (2016) · cites this paper as [29]
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Post-retrieval oxytocin facilitates next day extinction of threat memory in humans
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Navigating Central Oxytocin Transport: Known Realms and Uncharted Territories
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Understanding oxytocin in human physiology and pathophysiology: A path towards therapeutics
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Oral oxytocin delivery with proton pump inhibitor pretreatment decreases food intake
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LGR4 is essential for R-spondin1-mediated suppression of food intake via pro-opiomelanocortin
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Oxytocin modulates insulin and GLP-1 secretion in pancreatic islets
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Oxytocin increased intragastric pressure in the forestomach of rats via the dorsal vagal complex
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Effects of mesotocin manipulation on the behavior of male and female common waxbills
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- Authors
- Maejima, Y., Rita, R. S., Santoso, P., Aoyama, M., Hiraoka, Y., Nishimori, K., Gantulga, D., Shimomura, K., & Yada, T.
- Affiliations
- Jichi Medical University (JP)
- Utsunomiya University (JP)
- Tohoku University (JP)
- ORCID
- Venue
- Neuroendocrinology
- Publisher
- S. Karger AG
- Published
- 2015
- Volume
- 101
- Issue
- 1
- Pages
- 35-44
- ISSN
- 0028-3835 (ISSN-L)
- 1423-0194
- OpenAlex
- W1997601041
- Cited by
- 81
- References
- 50
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 4 · 2023: 6 · 2022: 5 · 2021: 6 · 2020: 8 · 2019: 9 · 2018: 12 · 2017: 6 · 2016: 10 · 2015: 4
- FWCI
- 5.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (15H02442, 26461366, 15K09395, 24591341)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- oxytocin, intranasal administration, intraperitoneal administration, dietary intake, hyperphagia, obesity, locomotor activity, glucose tolerance, glycemia, c-fos, paraventricular nucleus, area postrema, dorsal motor nucleus of the vagus, solitary tract nucleus, arcuate nucleus, insulin secretion, pancreatic islets, anorectic effect
- MeSH terms
- Administration, Intranasal, Animals, Blood Glucose, Brain, Eating, Glucose Tolerance Test, Male, Mice, Inbred C57BL, Motor Activity, Neurons, Oxytocin, Proto-Oncogene Proteins c-jun, Mice
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