Augmented orexin/hypocretin signaling underlies negative affect during acute oxycodone abstinence in rats.

Augmented orexin/hypocretin signaling underlies negative affect during acute oxycodone abstinence in rats. | 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 Augmented orexin/hypocretin signaling underlies negative affect during acute oxycodone abstinence in rats. Gary Aston-Jones, Kimberly Newman, Victoria Stiritz, Jeff Cheng, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7652324/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Opioid use disorder (OUD) is associated with a withdrawal-induced negative affective state, which contributes to uncontrolled use via negative reinforcement. The orexin (hypocretin) system is implicated in physical opioid withdrawal. We sought to test whether the orexin system is involved in negative affect during withdrawal from chronic prescription opioid exposure. Rats received non-contingent saline or oxycodone over 21d and were assessed for behaviors indicative of negative affect. We tested whether chronic oxycodone was associated with changes in orexin cell number or activity. We used chemogenetics in transgenic rats to modulate the activity of orexin neurons to determine their functional role in development of negative affect. Chronic oxycodone induced a negative affective state during acute abstinence that included relative weight loss, allodynia, and anhedonia-, anxiety, and despair-like behaviors. Oxycodone treatment was associated with an increase in the number and activity of orexin-immunoreactive neurons; the magnitude of negative affect severity directly correlated with the number of activated orexin neurons during acute abstinence. Chronic chemogenetic inhibition of orexin neurons concomitant with oxycodone exposure attenuated development of affective symptoms. Our data support a role for the orexin system in opioid withdrawal-associated negative affect and highlight this system as a potential treatment target for OUD. Biological sciences/Neuroscience/Reward Biological sciences/Neuroscience/Motivation Withdrawal depression anxiety opioid use disorder negative affect and hyperkatifeia. Full Text Additional Declarations There is NO Competing Interest. Cite Share Download PDF Status: Under Review 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-7652324","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":522947777,"identity":"00c46590-0a08-4235-9e2d-6640d21ad155","order_by":0,"name":"Gary 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