Pharmacological rescue of isolation-induced socialand neurochemical deficits in Drosophila melanogaster

Pharmacological rescue of isolation-induced socialand neurochemical deficits in Drosophila melanogaster | 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 Pharmacological rescue of isolation-induced socialand neurochemical deficits in Drosophila melanogaster Milan Petrović, Marta Medija, Lara Saftić Martinović, Ana Meštrović, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9227359/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Social isolation (ISO) is a major risk factor for mood disorders, reflected in disrupted neurochemistry and social behavior. Totest whether five days of ISO induce a depression-like state in Drosophila melanogaster, we measured brain monoaminesand social interaction networks (SINs), focusing on dopamine (DA) and octopamine (OA), key regulators of motivation andreward. ISO reduced DA, OA, and tyramine (TA) while increasing acetylcholine, and produced disorganized SINs marked byweaker, shorter interactions, reduced clustering and centrality, and hyperactive, uncoordinated locomotion. To test for rescue,flies were fed L-DA, OA, or both during ISO. All treatments improved monoamine levels, with the combined supplementationnormalizing or exceeding DA and OA and reducing acetylcholine to control levels. A condition-specific social interactionnetworks (SINs) metrics enabled consistent, quantitative comparisons across groups. SIN analyses showed that L-DA or OAalone partially restored connectivity among individuals, whereas combined supplementation most effectively rescued networkcohesion, clustering, and centrality, approaching or exceeding group-housed controls. Null-model comparisons confirmed thatthe restored networks reflected genuine, non-random structure rather than chance co-movement. Our findings show that fivedays of ISO induce neurochemical and behavioral changes in D. melanogaster that resemble depression, and that combinedDA+OA supplementation robustly restores monoaminergic balance and complex social organization. These results suggest amechanistic link between brain monoamines and group-level social behavior, highlighting the neurochemical basis of socialdeficits and their pharmacological rescue. Biological sciences/Neuroscience Biological sciences/Physiology Full Text Additional Declarations No competing interests reported. Supplementary Files Sicentificreportssuplement1.pdf Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 30 Apr, 2026 Reviews received at journal 29 Apr, 2026 Reviews received at journal 28 Apr, 2026 Reviewers agreed at journal 07 Apr, 2026 Reviewers agreed at journal 02 Apr, 2026 Reviewers invited by journal 01 Apr, 2026 Editor invited by journal 01 Apr, 2026 Editor assigned by journal 27 Mar, 2026 Submission checks completed at journal 27 Mar, 2026 First submitted to journal 25 Mar, 2026 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. 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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-9227359","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":616617077,"identity":"d1fba76e-fecf-4a7b-a8ec-c291fa01f23a","order_by":0,"name":"Milan 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