Effects of entinostat, quisinostat, and tubastatin-A on alcohol consumption in male high ethanol consuming rats
BackgroundThe 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 A...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Epigenetics and Epigenomics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/freae.2024.1503093/full |
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| author | Sheketha R. Hauser Sheketha R. Hauser Laura B. Ferguson Laura B. Ferguson Tiebing Liang Erin E. Jarvis R. Dayne Mayfield Richard L. Bell Richard L. Bell |
| author_facet | Sheketha R. Hauser Sheketha R. Hauser Laura B. Ferguson Laura B. Ferguson Tiebing Liang Erin E. Jarvis R. Dayne Mayfield Richard L. Bell Richard L. Bell |
| author_sort | Sheketha R. Hauser |
| collection | DOAJ |
| description | BackgroundThe 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.MethodAdult naïve male high alcohol drinking line 1 (HAD1) or alcohol-preferring (P) rats were given continuous 24-h, 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.ResultsIn HAD1 rats, entinostat reduced 2-, 4-, and 24-h ethanol intake across the 2nd – 5th test days; while, in P rats, entinostat’s effect was primarily seen at the 24-h time-point, at the highest dose and only across three test days. The high dose of quisinostat effectively reduced 24-h 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.ConclusionOverall, 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. |
| format | Article |
| id | doaj-art-6ffee9757d8f4f24b0ccb2a206015f88 |
| institution | Kabale University |
| issn | 2813-706X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Epigenetics and Epigenomics |
| spelling | doaj-art-6ffee9757d8f4f24b0ccb2a206015f882025-02-03T06:33:40ZengFrontiers Media S.A.Frontiers in Epigenetics and Epigenomics2813-706X2025-02-01210.3389/freae.2024.15030931503093Effects of entinostat, quisinostat, and tubastatin-A on alcohol consumption in male high ethanol consuming ratsSheketha R. Hauser0Sheketha R. Hauser1Laura B. Ferguson2Laura B. Ferguson3Tiebing Liang4Erin E. Jarvis5R. Dayne Mayfield6Richard L. Bell7Richard L. Bell8Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, United StatesPaul and Carole Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, United StatesWaggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX, United StatesDepartment of Neuroscience, University of Texas at Austin, Austin, TX, United StatesDepartment of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, United StatesWaggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX, United StatesDepartment of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, United StatesPaul and Carole Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, United StatesBackgroundThe 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.MethodAdult naïve male high alcohol drinking line 1 (HAD1) or alcohol-preferring (P) rats were given continuous 24-h, 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.ResultsIn HAD1 rats, entinostat reduced 2-, 4-, and 24-h ethanol intake across the 2nd – 5th test days; while, in P rats, entinostat’s effect was primarily seen at the 24-h time-point, at the highest dose and only across three test days. The high dose of quisinostat effectively reduced 24-h 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.ConclusionOverall, 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.https://www.frontiersin.org/articles/10.3389/freae.2024.1503093/fullalcoholalcohol-preferring P ratshigh alcohol drinking line-1 HAD-1 ratsentinostatquisinostattubastatin-A |
| spellingShingle | Sheketha R. Hauser Sheketha R. Hauser Laura B. Ferguson Laura B. Ferguson Tiebing Liang Erin E. Jarvis R. Dayne Mayfield Richard L. Bell Richard L. Bell Effects of entinostat, quisinostat, and tubastatin-A on alcohol consumption in male high ethanol consuming rats Frontiers in Epigenetics and Epigenomics alcohol alcohol-preferring P rats high alcohol drinking line-1 HAD-1 rats entinostat quisinostat tubastatin-A |
| title | Effects of entinostat, quisinostat, and tubastatin-A on alcohol consumption in male high ethanol consuming rats |
| title_full | Effects of entinostat, quisinostat, and tubastatin-A on alcohol consumption in male high ethanol consuming rats |
| title_fullStr | Effects of entinostat, quisinostat, and tubastatin-A on alcohol consumption in male high ethanol consuming rats |
| title_full_unstemmed | Effects of entinostat, quisinostat, and tubastatin-A on alcohol consumption in male high ethanol consuming rats |
| title_short | Effects of entinostat, quisinostat, and tubastatin-A on alcohol consumption in male high ethanol consuming rats |
| title_sort | effects of entinostat quisinostat and tubastatin a on alcohol consumption in male high ethanol consuming rats |
| topic | alcohol alcohol-preferring P rats high alcohol drinking line-1 HAD-1 rats entinostat quisinostat tubastatin-A |
| url | https://www.frontiersin.org/articles/10.3389/freae.2024.1503093/full |
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