Impact of brief maternal separation on rodent models of anergia induced by dopamine depletion: analysis in mice of both sexes during adulthood

Impact of brief maternal separation on rodent models of anergia induced by dopamine depletion: analysis in mice of both sexes during adulthood | 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 Impact of brief maternal separation on rodent models of anergia induced by dopamine depletion: analysis in mice of both sexes during adulthood Paula Matas-Navarro, Carla Carratalá-Ros, Andrea Martínez-Verdú, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7465702/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 20 Nov, 2025 Read the published version in Psychopharmacology → Version 1 posted You are reading this latest preprint version Abstract Mesolimbic dopamine (DA) regulates activation and effort in motivated behaviors. Impairments in DA function induce motivational symptoms such as anergia and fatigue seen in depression. Stress modulates DA depending on its duration and intensity. Early-life events such as maternal separation (MS) could act as stressors, affecting brain development and leading to behavioral changes later in life. However, little is known about the effect of early-life stressors on adult motivational processes and effort-based decision-making. CD1 male and female mice were subjected to early-mild MS (PND3-5, 90 min/day), and, during adulthood, were evaluated on selection of effortful responses under positive or aversive experimental conditions. The choice to engage in effortful activities such as running in a wheel versus engaging with passive reinforcers was evaluated in a three-choice-T-maze task. In the forced-swim task (FST), time dedicated to vigorously escaping versus passively floating was measured. MS mice of both sexes, spent more time in the RW, and climbing in the FST, showing an increase in relative preferences for activity-based reinforcers, and persistence in vigorous escaping from aversive contexts compared to non-separated mice. Separated animals were less anxious but males were less socially oriented. In adulthood, DA depletion induced anergic patterns both in the T-maze and in the FST only in males independently of separation conditions. Measures of anxiety, social interaction and sucrose preference and consumption were not affected after DA depletion. Thus, mild-early MS promotes effortful behaviors during adulthood in both sexes independently of the emotional value of the situation, but males were more vulnerable than females to DA-depletion induced-anergia. Early-life stress maternal separation dopamine behavioral activation sex differences Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementalmaterialMatasNavarroMS.pdf Cite Share Download PDF Status: Published Journal Publication published 20 Nov, 2025 Read the published version in Psychopharmacology → 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-7465702","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":515839645,"identity":"f0fea6c8-ddae-44a9-81a5-c05c6e2ffd92","order_by":0,"name":"Paula Matas-Navarro","email":"","orcid":"","institution":"Universitat Jaume I","correspondingAuthor":false,"prefix":"","firstName":"Paula","middleName":"","lastName":"Matas-Navarro","suffix":""},{"id":515839646,"identity":"49d371d2-a837-4e2b-bb7a-b06d22f35919","order_by":1,"name":"Carla Carratalá-Ros","email":"","orcid":"","institution":"Universitat Jaume I","correspondingAuthor":false,"prefix":"","firstName":"Carla","middleName":"","lastName":"Carratalá-Ros","suffix":""},{"id":515839649,"identity":"6e5783ed-64b4-4c1b-b633-244f77f80dfe","order_by":2,"name":"Andrea Martínez-Verdú","email":"","orcid":"","institution":"Universitat Jaume I","correspondingAuthor":false,"prefix":"","firstName":"Andrea","middleName":"","lastName":"Martínez-Verdú","suffix":""},{"id":515839650,"identity":"92e1a95c-d56d-4a13-b4d2-89cb38564d2d","order_by":3,"name":"John D. 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Impairments in DA function induce motivational symptoms such as anergia and fatigue seen in depression. Stress modulates DA depending on its duration and intensity. Early-life events such as maternal separation (MS) could act as stressors, affecting brain development and leading to behavioral changes later in life. However, little is known about the effect of early-life stressors on adult motivational processes and effort-based decision-making. CD1 male and female mice were subjected to early-mild MS (PND3-5, 90 min/day), and, during adulthood, were evaluated on selection of effortful responses under positive or aversive experimental conditions. The choice to engage in effortful activities such as running in a wheel versus engaging with passive reinforcers was evaluated in a three-choice-T-maze task. In the forced-swim task (FST), time dedicated to vigorously escaping versus passively floating was measured. MS mice of both sexes, spent more time in the RW, and climbing in the FST, showing an increase in relative preferences for activity-based reinforcers, and persistence in vigorous escaping from aversive contexts compared to non-separated mice. Separated animals were less anxious but males were less socially oriented. In adulthood, DA depletion induced anergic patterns both in the T-maze and in the FST only in males independently of separation conditions. Measures of anxiety, social interaction and sucrose preference and consumption were not affected after DA depletion. 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