Inhibition of oxytocin neurons during key periods of development has long-term behavioural and body composition effects | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Inhibition of oxytocin neurons during key periods of development has long-term behavioural and body composition effects Françoise Muscatelli, Fabienne Schaller, Marie-Sophie Alifrangis, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8223143/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Oxytocin (OT) is a neuromodulator of social behaviour in mammals and accumulative data support the concept of a critical period for OT action during infancy. However, it is possible that the specific functions of OT depend on different time periods of action. In this study, we aimed to determine whether there are developmental stages during which OT-expressing neurons play a decisive role with long-term consequences. To this end, we chemogenetically inhibited OT-expressing neurons during three critical periods of development (in infants, juveniles, and young adults) in male and female mice, followed by a longitudinal study to assess behaviour and metabolic perturbations. The most pronounced behavioural effects are observed after inhibition during infancy in both sexes. Notably, social memory is consistently impaired in males, regardless of the inactivation period. From a metabolic perspective, in adulthood, an increase in body weight is observed in all cohorts of males but fat mass and adipocyte size increase after inhibition of OT-expressing neurons during juvenile period. In addition, we observed a significant delay in the day of birth and an alteration in feeding behaviour in neonates after inhibiting OT-expressing neurons around the time of birth. Thus, inhibition of OT neurons during three postnatal periods has direct, distinct, and long-lasting consequences on social behaviour and metabolism, depending on the sex and on the timing of inactivation. Our results also demonstrate a role of foetal/neonate oxytocin neurons in the timing of birth and in early feeding behaviour. Health sciences/Diseases/Psychiatric disorders/Autism spectrum disorders Biological sciences/Neuroscience/Molecular neuroscience Full Text Additional Declarations The authors have declared there is NO conflict of interest to disclose Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8223143","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":552378303,"identity":"8cd22046-adb0-4aa1-bd84-49f4b81d69d9","order_by":0,"name":"Françoise Muscatelli","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0003-4001-6528","institution":"Institut de Neurobiologie de la Méditerranée (INMED), INSERM, Aix Marseille Université","correspondingAuthor":true,"prefix":"","firstName":"Françoise","middleName":"","lastName":"Muscatelli","suffix":""},{"id":552378304,"identity":"bdd768cf-5f5e-4af8-b74d-7f243f97afb1","order_by":1,"name":"Fabienne Schaller","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Fabienne","middleName":"","lastName":"Schaller","suffix":""},{"id":552378305,"identity":"3a1e4b9a-baea-4653-ba19-d5322e4665c5","order_by":2,"name":"Marie-Sophie Alifrangis","email":"","orcid":"","institution":"Institut de Neurobiologie de la Méditerranée (INMED), INSERM, Aix Marseille Université","correspondingAuthor":false,"prefix":"","firstName":"Marie-Sophie","middleName":"","lastName":"Alifrangis","suffix":""},{"id":552378306,"identity":"69ba5da0-4d40-4baf-9790-ba711e7822b2","order_by":3,"name":"Pierre-Yves Barelle","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Pierre-Yves","middleName":"","lastName":"Barelle","suffix":""},{"id":552378307,"identity":"5b918474-ba2a-41c6-ad69-242a90acab5f","order_by":4,"name":"Catarina Santos","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Catarina","middleName":"","lastName":"Santos","suffix":""},{"id":552378308,"identity":"4724b677-5f44-4206-9bf7-1f8e234c4cae","order_by":5,"name":"Roman Tyzio","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Roman","middleName":"","lastName":"Tyzio","suffix":""},{"id":552378309,"identity":"9a9cda41-fefe-424f-b061-54b669b438da","order_by":6,"name":"Alessandra Bertoni","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Alessandra","middleName":"","lastName":"Bertoni","suffix":""},{"id":552378310,"identity":"68a510da-6c6a-4464-971f-7bdec33d8cb9","order_by":7,"name":"Felix Omnes","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Felix","middleName":"","lastName":"Omnes","suffix":""},{"id":552378311,"identity":"2a65c361-2d50-432b-9498-200fbda402a9","order_by":8,"name":"Yasmine Belaidouni","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Yasmine","middleName":"","lastName":"Belaidouni","suffix":""},{"id":552378312,"identity":"8d881f96-56bb-4c04-9cbb-a8fef81e6aa5","order_by":9,"name":"Francesca Bader","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Francesca","middleName":"","lastName":"Bader","suffix":""},{"id":552378313,"identity":"501f58ad-5cbb-41eb-918e-5316d07bda11","order_by":10,"name":"Emilie Pallesi-Pocachard","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Emilie","middleName":"","lastName":"Pallesi-Pocachard","suffix":""},{"id":552378314,"identity":"744705db-c35b-4fb0-84ed-08e96c1d53d6","order_by":11,"name":"jean-luc Gaiarsa","email":"","orcid":"https://orcid.org/0000-0001-7354-0559","institution":"Institut de Neurobiologie de la Méditerranée","correspondingAuthor":false,"prefix":"","firstName":"jean-luc","middleName":"","lastName":"Gaiarsa","suffix":""},{"id":552378315,"identity":"83dcc050-dc27-4615-bb58-dcff1fbdf4f7","order_by":12,"name":"Sebastien Bouret","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Sebastien","middleName":"","lastName":"Bouret","suffix":""}],"badges":[],"createdAt":"2025-11-27 14:45:44","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8223143/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8223143/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":97104497,"identity":"8d2b3d97-4958-4391-a986-a25fbba21ab0","added_by":"auto","created_at":"2025-12-01 04:13:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1953093,"visible":true,"origin":"","legend":"","description":"","filename":"Schalleretal.FullManuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8223143/v1/dad75ddafd4700222cd4599c.pdf"},{"id":97104496,"identity":"c4550754-6007-4091-9e68-9315921e19f0","added_by":"auto","created_at":"2025-12-01 04:13:07","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":13660,"visible":true,"origin":"","legend":"","description":"","filename":"2025TP002926.json","url":"https://assets-eu.researchsquare.com/files/rs-8223143/v1/4486c97534c0bc1e7abf445c.json"},{"id":103050127,"identity":"d90184e3-eb35-4de1-adf0-dc9aa41c5da2","added_by":"auto","created_at":"2026-02-20 07:48:22","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1948433,"visible":true,"origin":"","legend":"Article File","description":"","filename":"Schalleretal.FullManuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8223143/v1_covered_152500f4-6fa2-4efa-8298-00952e157009.pdf"}],"financialInterests":"The authors have declared there is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose","formattedTitle":"Inhibition of oxytocin neurons during key periods of development has long-term behavioural and body composition effects","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8223143/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8223143/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eOxytocin (OT) is a neuromodulator of social behaviour in mammals and accumulative data support the concept of a critical period for OT action during infancy. However, it is possible that the specific functions of OT depend on different time periods of action.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn this study, we aimed to determine whether there are developmental stages during which OT-expressing neurons play a decisive role with long-term consequences. To this end, we chemogenetically inhibited OT-expressing neurons during three critical periods of development (in infants, juveniles, and young adults) in male and female mice, followed by a longitudinal study to assess behaviour and metabolic perturbations. The most pronounced behavioural effects are observed after inhibition during infancy in both sexes. Notably, social memory is consistently impaired in males, regardless of the inactivation period. From a metabolic perspective, in adulthood, an increase in body weight is observed in all cohorts of males but fat mass and adipocyte size increase after inhibition of OT-expressing neurons during juvenile period. In addition, we observed a significant delay in the day of birth and an alteration in feeding behaviour in neonates after inhibiting OT-expressing neurons around the time of birth.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThus, inhibition of OT neurons during three postnatal periods has direct, distinct, and long-lasting consequences on social behaviour and metabolism, depending on the sex and on the timing of inactivation. Our results also demonstrate a role of foetal/neonate oxytocin neurons in the timing of birth and in early feeding behaviour.\u003c/p\u003e","manuscriptTitle":"Inhibition of oxytocin neurons during key periods of development has long-term behavioural and body composition effects","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-01 04:13:02","doi":"10.21203/rs.3.rs-8223143/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"
[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"82a9142d-dd9c-45d5-adc3-b49411e3d97c","owner":[],"postedDate":"December 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":58785448,"name":"Health sciences/Diseases/Psychiatric disorders/Autism spectrum disorders"},{"id":58785449,"name":"Biological sciences/Neuroscience/Molecular neuroscience"}],"tags":[],"updatedAt":"2026-02-19T12:26:04+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-01 04:13:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8223143","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8223143","identity":"rs-8223143","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}
Text is read by the "Ask this paper" AI Q&A widget below.
Extraction quality varies by source — PMC NXML preserves structure
cleanly, OA-HTML may include some navigation residue, and OA-PDF can
have broken hyphenation. The publisher copy
(via DOI)
is the canonical version.