{"id":556734,"date":"2023-02-25T14:08:27","date_gmt":"2023-02-25T11:08:27","guid":{"rendered":"https:\/\/en.buradabiliyorum.com\/a-new-epigenetic-brain-defense-against-recurrence-of-opioid-use\/"},"modified":"2023-02-25T14:08:27","modified_gmt":"2023-02-25T11:08:27","slug":"a-new-epigenetic-brain-defense-against-recurrence-of-opioid-use","status":"publish","type":"post","link":"https:\/\/buradabiliyorum.com\/en\/a-new-epigenetic-brain-defense-against-recurrence-of-opioid-use\/","title":{"rendered":"#A new epigenetic brain defense against recurrence of opioid use"},"content":{"rendered":"<div id=\"ez-toc-container\" class=\"ez-toc-v2_0_85 counter-hierarchy ez-toc-counter ez-toc-custom ez-toc-container-direction\">\n<p class=\"ez-toc-title\" style=\"cursor:inherit\">Table of Contents<\/p>\n<label for=\"ez-toc-cssicon-toggle-item-6a4129e8720f2\" class=\"ez-toc-cssicon-toggle-label\"><span class=\"\"><span class=\"eztoc-hide\" style=\"display:none;\">Toggle<\/span><span class=\"ez-toc-icon-toggle-span\"><svg style=\"fill: #dd3333;color:#dd3333\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\" class=\"list-377408\" width=\"20px\" height=\"20px\" viewBox=\"0 0 24 24\" fill=\"none\"><path d=\"M6 6H4v2h2V6zm14 0H8v2h12V6zM4 11h2v2H4v-2zm16 0H8v2h12v-2zM4 16h2v2H4v-2zm16 0H8v2h12v-2z\" fill=\"currentColor\"><\/path><\/svg><svg style=\"fill: #dd3333;color:#dd3333\" class=\"arrow-unsorted-368013\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\" width=\"10px\" height=\"10px\" viewBox=\"0 0 24 24\" version=\"1.2\" baseProfile=\"tiny\"><path d=\"M18.2 9.3l-6.2-6.3-6.2 6.3c-.2.2-.3.4-.3.7s.1.5.3.7c.2.2.4.3.7.3h11c.3 0 .5-.1.7-.3.2-.2.3-.5.3-.7s-.1-.5-.3-.7zM5.8 14.7l6.2 6.3 6.2-6.3c.2-.2.3-.5.3-.7s-.1-.5-.3-.7c-.2-.2-.4-.3-.7-.3h-11c-.3 0-.5.1-.7.3-.2.2-.3.5-.3.7s.1.5.3.7z\"\/><\/svg><\/span><\/span><\/label><input type=\"checkbox\"  id=\"ez-toc-cssicon-toggle-item-6a4129e8720f2\" checked aria-label=\"Toggle\" \/><nav><ul class='ez-toc-list ez-toc-list-level-1 ' ><li class='ez-toc-page-1 ez-toc-heading-level-1'><a class=\"ez-toc-link ez-toc-heading-1\" href=\"https:\/\/buradabiliyorum.com\/en\/a-new-epigenetic-brain-defense-against-recurrence-of-opioid-use\/#%E2%80%9CA_new_epigenetic_brain_defense_against_recurrence_of_opioid_use%E2%80%9D\" >&#8220;A new epigenetic brain defense against recurrence of opioid use&#8221;<\/a><\/li><\/ul><\/nav><\/div>\n<h1><span class=\"ez-toc-section\" id=\"%E2%80%9CA_new_epigenetic_brain_defense_against_recurrence_of_opioid_use%E2%80%9D\"><\/span>&#8220;A new epigenetic brain defense against recurrence of opioid use&#8221;<span class=\"ez-toc-section-end\"><\/span><\/h1>\n<div>\n<div class=\"article-gallery lightGallery\">\n<div data-thumb=\"https:\/\/scx1.b-cdn.net\/csz\/news\/tmb\/2023\/a-new-epigenetic-brain.jpg\" data-src=\"https:\/\/scx2.b-cdn.net\/gfx\/news\/hires\/2023\/a-new-epigenetic-brain.jpg\" data-sub-html=\"Wild-type HDAC5 (red) located in the cytoplasm of a rat nucleus accumbens medium spiny neuron. Credit: Medical University of South Carolina, Dr. Christopher Cowan\">\n<figure class=\"article-img\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/scx1.b-cdn.net\/csz\/news\/800a\/2023\/a-new-epigenetic-brain.jpg\" alt=\"A new epigenetic brain defense against recurrence of opioid use\" title=\"Wild-type HDAC5 (red) located in the cytoplasm of a rat nucleus accumbens medium spiny neuron. Credit: Medical University of South Carolina, Dr. Christopher Cowan\" width=\"800\" height=\"530\"\/><figcaption class=\"text-darken text-low-up text-truncate-js text-truncate mt-3\">\n                Wild-type HDAC5 (red) located in the cytoplasm of a rat nucleus accumbens medium spiny neuron. Credit: Medical University of South Carolina, Dr. Christopher Cowan<br \/>\n            <\/figcaption><\/figure>\n<\/div>\n<\/div>\n<p>Substance use disorder (SUD) is an extremely difficult disorder to overcome, and many individuals with SUD return to regular use after repeated attempts to quit.\n                                                <\/p>\n<p>A return to regular drug use can be caused by the body&#8217;s physical dependence on the drug as well as experiences associated with prior drug use. Exactly how these drug associations are formed in the brain and how they trigger a return to drug use remain unclear.<\/p>\n<p>&#8220;Individuals make long-lasting associations between the euphoric experience of the drug and the people, places and things associated with drug use,&#8221; said Christopher Cowan, Ph.D. professor in the Department of Neuro<a href=\"https:\/\/buradabiliyorum.com\/en\/category\/sciencee\/\" data-internallinksmanager029f6b8e52c=\"5\" title=\"Science\" target=\"_blank\" rel=\"noopener\">science<\/a> at the Medical University of South Carolina (MUSC) and member of the Brain and Behavior Research Foundation Scientific Council.<\/p>\n<p>Cowan and his team report in the <i>Proceedings of the National Academy of Sciences<\/i> that an enzyme known as histone deacetylase 5, or HDAC5, plays a significant role in limiting heroin-associated memories and drug-seeking behavior following a period of abstinence in rats.<\/p>\n<p>The study reveals HDAC5 as a target of interest in treating vulnerability to return to drug use in opioid use disorder.<\/p>\n<p>HDAC5 is an &#8220;epigenetic&#8221; enzyme, meaning it can influence the expression of many different genes. HDAC5 is active in the brain and has been associated previously with resumed cocaine use after a period of abstinence.<\/p>\n<p>&#8220;In a prior study, we showed that HDAC5 is regulated by cocaine, and it reduces the impact of substance use triggers following cocaine use,&#8221; said Cowan. &#8220;In the new study, we wanted to learn why HDAC5 had these effects and if they were specific to cocaine or perhaps <a href=\"https:\/\/buradabiliyorum.com\/en\/category\/general\/\" data-internallinksmanager029f6b8e52c=\"3\" title=\"General\" target=\"_blank\" rel=\"noopener\">general<\/a>izable to other classes of addictive drugs, like opioids.&#8221;<\/p>\n<p>Cowan examined drug-seeking behaviors by modelling a return to opioid use in rats after a period of abstinence from self-administration of heroin, a commonly used opioid drug.<\/p>\n<p>First, rats were given the opportunity to self-administer heroin by pressing a lever. At the same time, they were presented with visual and audio cues that they associated with their heroin use.<\/p>\n<p>Then, after 2-3 weeks of daily heroin use, the rats went through a week of abstinence before being placed back in the environment where they formerly used heroin. This drug-associated &#8220;place&#8221; triggered the pressing of the lever, or heroin seeking, but in this case no heroin was delivered.<\/p>\n<p>                                            <!-- Google middle Adsense block -->\n    <\/p>\n<p>Later, drug-seeking behavior was stimulated in the rats by exposing them to the visual and audio cues formerly linked to their heroin use.<\/p>\n<p>Finally, the rats were given a small dose of heroin to remind them of the feeling of the drug, and again, this stimulated vigorous heroin seeking.<\/p>\n<p>&#8220;By seeing how many times the rats press the lever while not getting the drug, we can measure the strength of the drug-use context, the drug-associated memory cues or the re-exposure to physiological drug effects to promote return to heroin use,&#8221; explained Cowan.<\/p>\n<p>To see how HDAC5 controlled drug-seeking behavior after a period of abstinence, Cowan&#8217;s lab used a molecular trick to either increase or decrease the levels of HDAC5 in the nucleus, or DNA-containing site, of their targeted brain cells.<\/p>\n<p>Rats with lower HDAC5 showed enhanced heroin seeking when exposed to triggers, while rats with higher HDAC5 showed reduced heroin-seeking behavior. This finding showed that the epigenetic enzyme HDAC5 plays a critical role in modulating the power of drug-associated memories and preventing a return to drug use.<\/p>\n<p>&#8220;We found that HDAC5 limits heroin-associated cues and opposes the powerful nature of these drug cues to trigger drug-seeking behavior,&#8221; said Cowan. &#8220;This suggests that, in the brain, HDAC5 functions to influence the formation and strength of these drug memories that can promote a return to drug use.&#8221;<\/p>\n<p>To ensure that their findings were specific to drug-seeking behavior and not just general reward seeking, Cowan&#8217;s lab repeated the same experiment but used sucrose instead of heroin. Sucrose is a simple sugar that rats enjoy consuming and serves as a natural reward.<\/p>\n<p>&#8220;There was absolutely no effect of HDAC5 on sucrose-seeking behavior,&#8221; said Cowan. &#8220;So, it seems that addictive drugs, like cocaine and heroin, are engaging HDAC5 in a way that is separate from our natural reward learning and memory process.&#8221;<\/p>\n<p>After observing the effects of HDAC5 on drug-seeking behavior, Cowan&#8217;s lab investigated what genes HDAC5 was actually controlling.<\/p>\n<p>&#8220;We found hundreds of genes affected by HDAC5,&#8221; said Cowan. &#8220;But a large number of the genes are linked to ion channels that influence the excitability of neuronal cells in the brain.&#8221;<\/p>\n<p>Rats with higher levels of HDAC5 had much less excitable neurons than those with low HDAC5, showing that the enzyme has a suppressive effect.<\/p>\n<p>&#8220;The firing suppression from HDAC5 is likely a key underlying mechanism controlling the formation and strength of drug-associated memories,&#8221; said Cowan.<\/p>\n<p>With a better understanding at a molecular level of drug addiction and return to drug use, scientists and physicians can develop targeted therapies to treat SUD. Future studies in Cowan&#8217;s lab aim to leverage HDAC5 to make the road to recovery less challenging.<\/p>\n<p>&#8220;We have uncovered a mechanism in the brain that is controlling the formation and maintenance of really powerful and enduring drug-cue associations,&#8221; said Cowan. &#8220;We want to translate these findings to the clinic and help individuals with substance use disorder by reducing vulnerability to return to regular drug use.&#8221;<\/p>\n<div class=\"article-main__more p-4\">\n<p><strong>More information:<\/strong><br \/>\n                                                    Ethan M. Anderson et al, Epigenetic function during heroin self-administration controls future relapse-associated behavior in a cell type-specific manner, <i>Proceedings of the National Academy of Sciences<\/i> (2023).  <a rel=\"nofollow noopener\" target=\"_blank\" data-doi=\"1\" href=\"https:\/\/dx.doi.org\/10.1073\/pnas.2210953120\">DOI: 10.1073\/pnas.2210953120<\/a><\/p><\/div>\n<div class=\"d-inline-block text-medium my-4\">\n                                                Provided by<br \/>\n                                                                                                    Medical University of South Carolina<br \/>\n                                                                                                        <a rel=\"nofollow noopener\" target=\"_blank\" class=\"icon_open\" href=\"http:\/\/academicdepartments.musc.edu\/musc\/\"><br \/>\n                                                        <svg><use href=\"https:\/\/medx.b-cdn.net\/tmpl\/v6\/img\/svg\/sprite.svg#icon_open\" x=\"0\" y=\"0\"\/><\/svg><\/a><\/p><\/div>\n<p>                                        <!-- print only --><\/p>\n<div class=\"d-none d-print-block\">\n<p>                                                 <strong>Citation<\/strong>:<br \/>\n                                                 A new epigenetic brain defense against recurrence of opioid use (2023, February 25)<br \/>\n                                                 retrieved 26 February 2023<br \/>\n                                                 from https:\/\/medicalxpress.com\/<a href=\"https:\/\/buradabiliyorum.com\/en\/category\/news\/\" data-internallinksmanager029f6b8e52c=\"2\" title=\"News\" target=\"_blank\" rel=\"noopener\">news<\/a>\/2023-02-epigenetic-brain-defense-recurrence-opioid.html<\/p>\n<p>                                            This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no<br \/>\n                                            part may be reproduced without the written permission. The content is provided for information purposes only.<\/p><\/div>\n<\/p><\/div>\n<p><script id=\"facebook-jssdk\" async=\"\" src=\"https:\/\/connect.facebook.net\/en_US\/sdk.js\"><\/script><\/p>\n<blockquote><p><strong><span style=\"color: #ff6600;\">If you liked the article, do not forget to share it with your friends. Follow us on\u00a0<span style=\"color: #ff0000;\"><a style=\"color: #ff0000;\" href=\"https:\/\/news.google.com\/publications\/CAAqBwgKMLG0nwswvr63Aw\" target=\"_blank\" rel=\"nofollow noopener noreferrer\">Google News<\/a><\/span>\u00a0too, click on the star and choose us from your favorites.<\/span><\/strong><\/p><\/blockquote>\n<blockquote>\n<p style=\"text-align: center;\">For forums sites go to <span style=\"color: #ff9900;\"><a style=\"color: #ff9900;\" href=\"https:\/\/forum.buradabiliyorum.com\/\" target=\"_blank\" rel=\"noopener\">Forum.BuradaBiliyorum.Com<\/a><\/span><\/strong>\n<\/p><\/blockquote>\n<blockquote>\n<p style=\"text-align: center;\"><strong>If you want to read more Like this articles, you can visit our <span style=\"color: #ff9900;\"><a style=\"color: #ff9900;\" href=\"https:\/\/en.buradabiliyorum.com\/science\/\" target=\"_blank\" rel=\"noopener\">Science category.<\/a><\/span><\/strong><\/p>\n<\/blockquote>\n<p><span style=\"color: black;\"><a style=\"color: #ff9900;\" href=\"https:\/\/medicalxpress.com\/news\/2023-02-epigenetic-brain-defense-recurrence-opioid.html\" target=\"_blank\" rel=\"noopener\">Source<\/a><\/span><\/p>\n","protected":false},"excerpt":{"rendered":"<p>&#8220;A new epigenetic brain defense against recurrence of opioid use&#8221; Wild-type HDAC5 (red) located in the cytoplasm of a rat nucleus accumbens medium spiny neuron. Credit: Medical University of South Carolina, Dr. Christopher Cowan Substance use disorder (SUD) is an extremely difficult disorder to overcome, and many individuals with SUD return to regular use after&#8230;<\/p>\n","protected":false},"author":1,"featured_media":556735,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"fifu_image_url":"https:\/\/scx2.b-cdn.net\/gfx\/news\/hires\/2023\/a-new-epigenetic-brain.jpg","fifu_image_alt":"","footnotes":""},"categories":[16],"tags":[],"class_list":["post-556734","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-sciencee"],"_links":{"self":[{"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/posts\/556734","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/comments?post=556734"}],"version-history":[{"count":0,"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/posts\/556734\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/media\/556735"}],"wp:attachment":[{"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/media?parent=556734"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/categories?post=556734"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/tags?post=556734"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}