Overeating in the Ts65Dn trisomic mouse model is associated with dopaminergic neurotransmission deficit in the prefrontal cortex

Overeating in the Ts65Dn trisomic mouse model is associated with dopaminergic neurotransmission deficit in the prefrontal cortex | 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 Research Article Overeating in the Ts65Dn trisomic mouse model is associated with dopaminergic neurotransmission deficit in the prefrontal cortex Marta Fructuoso, Alvaro Fernandez-Blanco, Ana Gallego, Maria Martínez de Lagrán, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2358600/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 Individuals with Down syndrome (DS) have a higher prevalence of obesity than the general population. This has traditionally been attributed to endocrine issues and deficient exercise. However, the development of obesity is coupled with deficits in neural reward responses, and previous works showed dopaminergic disturbances in DS. We here tested the hypothesis that “hedonic” overeating may play a central role in the development of obesity as a consequence of sub-functional dopaminergic neurotransmission in a mouse model that bears in triplicate many most of the genes in trisomy 21, Ts65Dn. Meal pattern analysis in this trisomic mouse model (Ts65Dn), revealed an increased preference for energy-dense food. Trisomic mice also scored significantly higher in compulsivity and inflexibility tests as measured by limited access to energy-dense food and food adulteration with quinine hydrochloride. We detected reduced dopamine levels in the prefrontal cortex of Ts65Dn mice, and insensitivity to the dopamine D2receptor agonist (quinpirole) anorectic effect for palatable foods that may facilitate overeating in an attempt to restore optimal dopamine levels. Interestingly, impulsive and compulsive behaviors were significantly reduced when prelimbic-to-nucleus accumbens projections were activated in Ts65Dn mice using a chemogenetic approach. Our work unravels a new mechanism underlying vulnerability to the development of overeating in DS, which could pave the way towards novel and efficient interventions for obesity. Down syndrome obesity overeating prefrontal cortex dopamine Full Text Supplementary Files DataFructuosoetal2022.xlsx 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-2358600","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":161689180,"identity":"b81ec08e-0e40-4041-9140-fdf2103845d8","order_by":0,"name":"Marta Fructuoso","email":"","orcid":"","institution":"ICM: Institut du cerveau et de la moelle epiniere","correspondingAuthor":false,"prefix":"","firstName":"Marta","middleName":"","lastName":"Fructuoso","suffix":""},{"id":161689181,"identity":"ee550e8e-0419-4b8d-ae7c-a25cd43bc2f4","order_by":1,"name":"Alvaro Fernandez-Blanco","email":"","orcid":"","institution":"Centre de Regulació 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