Dopamine receptor 1-expressing cells in the ventral hippocampus encode cocaine-context associations

Dopamine receptor 1-expressing cells in the ventral hippocampus encode cocaine-context associations | 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 Dopamine receptor 1-expressing cells in the ventral hippocampus encode cocaine-context associations Eric Nestler, Veronika Kondev, Arthur Godino, Brian Kipp, Evelyn Hennigan, and 15 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8079719/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 Dopamine (DA) signaling facilitates emotional valence, reward prediction error, and motivation; thus, dysfunctional dopamine signaling has been tied to several neuropsychiatric disorders, including substance use disorder (SUD). While most research has focused on striatal DA signaling, we and others have established that the ventral hippocampus (vHPC) also exhibits topographical organization of mostly non-overlapping dopaminoceptive neuronal populations: those expressing the DA receptor type 1 (D1) or type 2 (D2). Here, we use fiber photometry, optogenetics, and single nuclei RNA-sequencing (snRNA-seq) to explore how dopaminoceptive cells in the vHPC control cocaine-context memory expression. We reveal that vHPC D1 cells are inhibited by cocaine-conditioned contextual cues and that this inhibition is necessary and sufficient for reward-context associations driving cocaine conditioned place preference (CPP). Meanwhile vHPC D2 cells are not dynamically altered by learning but rather support positive reinforcement. Transcriptional changes induced by cocaine CPP encode these distinct functions, with D1 cells undergoing the greatest gene expression changes tied to synaptic signaling and plasticity. Together, these studies broaden our understanding of the role of DA within the larger mesocorticolimbic system and reveal new neuronal and circuit mechanisms underlying how drugs of abuse promote strong associative learning that could drive compulsive drug seeking characteristic of SUD. Biological sciences/Neuroscience/Motivation Biological sciences/Neuroscience/Reward Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryFigures.pdf Supplementary Material 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. 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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-8079719","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":545236493,"identity":"ee32c786-bbfb-495c-adf3-8dd8a208a5a8","order_by":0,"name":"Eric 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