Drug Abstinence Changes Gene Expression, Making Relapse More Likely

prolonged abstinence “The novelty of our current paper is that it begins to reveal what happens on a cellular basis, what genes are turned on and off during a prolonged period of abstinence,” said David M. Dietz, PhD, senior author and chair of the Department of Pharmacology and Toxicology. The research focused on the nucleus accumbens, a center of reward and motivation in the brain. The researchers looked specifically at molecules known as chromatin remodelers that can facilitate or prevent access to DNA, ultimately affecting gene expression. They found that chromatin remodeler INO80 causes changes in gene expression that enhances cocaine-craving behavior. While after one day of abstinence from cocaine there was no change in expression of INO80, there was a significant increase after 30 days of abstinence. The findings also reveal how a class of proteins called E3 ubiquitin ligases facilitates relapse. Currently the subject of well-funded research in the pharmaceutical industry for psychiatric and neurologic diseases, E3 ubiquitin ligase proteins have yet to be well-explored in terms of their relevance to addiction and relapse. Last year, Werner and his colleagues at UB published the first paper regarding another one of these proteins and its role in addiction and relapse. The current UB study reveals that an E3 ubiquitin ligase called TRIM3 tags INO80 with a ubiquitin chain indicating to the cell to degrade INO80. The researchers found that a decrease in TRIM3 likely underlies the observed increase in INO80 (less TRIM3 means less INO80 being degraded). Increased drug craving “When there’s less TRIM3 and more INO80, that leads to an increase in drug craving,” said Werner, “but when there’s more TRIM3 and less INO80, drug-craving behavior is reduced.” They found this effect whether they manipulated INO80 directly, or through the alterations of TRIM3 levels, he said. “INO80 affects some combination of target genes,” said Werner. “In the future, we want to find out which of those downstream genes are contributing to drug-craving behaviors. This would be a big first step into this really new territory of how gene expression maintains relapse https://www.technologynetworks.com/genomics/news/drug-abstinence-changes-gene-expression-making-relapse-more-likely-325007?utm_campaign=NEWSLETTER_TN_Breaking%20Science%20News&utm_source=hs_email&utm_medium=email&utm_content=77906125&_hsenc=p2ANqtz-_45dRrGuKf0380b4bbq5aK1MhmjqD0QXrjFYGaN2sAX32wtw4I2YLiX29AuE8kyRpECmoz8HWvFGdxR9WEt0PzMrJm-A&_hsmi=77906125