Involvement of Adenozine A2a Receptors in Anxiety-like Behaviors in Tetrahydrocannabinol Treated Mice

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Abstract Previous studies have suggested that adenosinergic system in the central nervous system, may play a role in both behavioral changes and the physiopathology induced by Δ9-tetrahydrocannabinol (THC), and this is thought to be mediated by adenosine A₂A receptors (A₂AR). However, the contribution of the adenosinergic system to the anxiety-like behaviors in response to THC in mice is not well understood. In this study, we aimed to investigate the possible role of the adenosinergic system in THC-treated mice. For that purpose, we combined behavioral tests and molecular analyses to investigate the effects of THC, in relation with the agonist and antagonist of the adenosinergic system, CGS-21680 (CGS) and Istradefylline, respectively, on both anxiety-like behaviors and hippocampal gene expression. The results demonstrated that THC induced anxiety-like behavior, and gene expression patterns indicated a significant interaction between the adenosinergic and cannabinoidergic systems. Notably, the data suggests that THC plays a predominant role in this molecular interplay, with its effects being partially modulated by changes in the expression of both cannabinoidergic and adenosinergic receptors, CB₁R and Adora2a (A₂AR), respectively. These findings contribute to the understanding of THC's complex pharmacological actions, highlighting the importance of receptor cross-talk in modulating anxiety and other behavioral outcomes.
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Involvement of Adenozine A2a Receptors in Anxiety-like Behaviors in Tetrahydrocannabinol Treated Mice | 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 Involvement of Adenozine A2a Receptors in Anxiety-like Behaviors in Tetrahydrocannabinol Treated Mice Burçin Ün, Zeki Akarsakarya, Özlem Yorulmaz Özü, Nermin Seda Ilgaz, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3991109/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Abstract Previous studies have suggested that adenosinergic system in the central nervous system, may play a role in both behavioral changes and the physiopathology induced by Δ9-tetrahydrocannabinol (THC), and this is thought to be mediated by adenosine A₂A receptors (A₂AR). However, the contribution of the adenosinergic system to the anxiety-like behaviors in response to THC in mice is not well understood. In this study, we aimed to investigate the possible role of the adenosinergic system in THC-treated mice. For that purpose, we combined behavioral tests and molecular analyses to investigate the effects of THC, in relation with the agonist and antagonist of the adenosinergic system, CGS-21680 (CGS) and Istradefylline, respectively, on both anxiety-like behaviors and hippocampal gene expression. The results demonstrated that THC induced anxiety-like behavior, and gene expression patterns indicated a significant interaction between the adenosinergic and cannabinoidergic systems. Notably, the data suggests that THC plays a predominant role in this molecular interplay, with its effects being partially modulated by changes in the expression of both cannabinoidergic and adenosinergic receptors, CB₁R and Adora2a (A₂AR), respectively. These findings contribute to the understanding of THC's complex pharmacological actions, highlighting the importance of receptor cross-talk in modulating anxiety and other behavioral outcomes. Adenosine A2A receptors Anxiety-like behaviors Hippocampus Tetrahydrocannabinol Full Text Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 2 posted You are reading this latest preprint version Show more versions 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. 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