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ORIGINAL RESEARCH article

Front. Epigenet. Epigenom.
Sec. Chromatin Epigenomics
Volume 2 - 2024 | doi: 10.3389/freae.2024.1503093

Effects of Entinostat, Quisinostat, and Tubastatin-A on Alcohol Consumption in Male High Ethanol Consuming Rats

Provisionally accepted
Sheketha R Hauser Sheketha R Hauser 1,2*Laura B Ferguson Laura B Ferguson 3,4Tiebing Liang Tiebing Liang 5Erin E. Jarvis Erin E. Jarvis 6R. Dayne Mayfield R. Dayne Mayfield 3Richard L Bell Richard L Bell 1,2
  • 1 Department of Psychiatry, School of Medicine, Indiana University Bloomington, Suite, Indiana, United States
  • 2 Stark Neurosciences Research Institute, School of Medicine, Indiana University Bloomington, Indianapolis, Indiana, United States
  • 3 Waggoner Center for Alcohol and Addiction Research, College of Natural Sciences, The University of Texas at Austin, Austin, Texas, United States
  • 4 Department of Neuroscience, College of Natural Sciences, The University of Texas at Austin, Austin, Texas, United States
  • 5 Department of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Indinapolois, United States
  • 6 Department of Pediatrics, School of Medicine, Indiana University Bloomington, Indianapolis, Indiana, United States

The final, formatted version of the article will be published soon.

    Background: The interaction between genetics, epigenetics, and the environment plays a key role in the development of alcohol use disorder (AUD). Pharmacological treatments targeting histone deacetylases (HDACs) suggest that HDAC inhibitors (HDACi) may be potential pharmacotherapeutic treatments for AUD. The objective of the current study was to test the effects of different HDACi on ethanol intake in two rat lines selectively bred for high ethanol-consumption. Method: Adult naïve male high alcohol drinking line 1 (HAD1) or alcohol-preferring (P) rats were given continuous 24-hour, 3-bottle, free-choice access to 15%, 30% ethanol concurrently with water for 8 weeks prior to testing entinostat (selective HDAC1i and HADC3i, 0, 1.25, 2.5, 5 mg/kg, i.p.), quisinostat (pan HADCi, 0, 0.5, 1.0, 2.0 mg/kg, i.p.), or tubastatin-A (selective HDAC6i, 0, 1.25, 2.5, 5 mg/kg, i.p.) over 4-5 consecutive days. Results: In HAD1 rats, entinostat reduced 2-, 4-, and 24-hour ethanol intake across the 2nd – 5th test days; while, in P rats, entinostat’s effect was primarily seen at the 24-hour time-point, at the highest dose and only across 3 test days. The high dose of quisinostat effectively reduced 24-hour ethanol intake across the 1st—4th test days in HAD1 rats but was ineffective in P rats. Tubastatin-A did not alter ethanol intake in either rat line. Conclusion: Overall, the results confirmed that a pan and a more selective (HDAC1 and HDAC3) HDACi effectively reduced ethanol intake in HAD1, while only the more selective HDACi reduced ethanol intake in P rats. Inhibition of HDAC6 does not appear to regulate ethanol intake in HAD1 or P rats.

    Keywords: alcohol, Alcohol-Preferring P rats, High Alcohol Drinking Line-1 HAD-1 rats, Entinostat, Quisinostat, Tubastatin-A, epigenetics, HDAC inhibitors

    Received: 28 Sep 2024; Accepted: 19 Dec 2024.

    Copyright: © 2024 Hauser, Ferguson, Liang, Jarvis, Mayfield and Bell. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Sheketha R Hauser, Department of Psychiatry, School of Medicine, Indiana University Bloomington, Suite, 5100, Indiana, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.