The Class I-Specific HDAC Inhibitor MS-275 Decreases Motivation to Consume Alcohol and Relapse in Heavy Drinking Rats

The International Journal of Neuropsychopharmacology
Jerome JeanblancMickaël Naassila

Abstract

New strategies for the treatment of alcohol dependence are a pressing need, and recent evidence suggests that targeting enzymes involved in epigenetic mechanisms seems to have great potential. Among these mechanisms, alteration of histone acetylation by histone deacetylases is of great importance for gene expression and has also been implicated in addiction. Here, we examined whether intra-cerebroventricular administration of MS-275, a class I-specific histone deacetylase inhibitor, could alter ethanol self-administration, motivation to consume ethanol, and relapse in heavy drinking rats. Male Long Evans rats trained to self-administer high levels of ethanol received intra-cerebroventricular micro-infusions of MS-275 (250 µM, 500 µM, and 1000 µM) 3 hours prior to the self-administration sessions. First, we demonstrated that intra-cerebroventricular infusion of MS-275 increases acetylation of Histone 4 within the nucleus accumbens nucleus accumbens and the dorsolateral striatum. Second, we observed that MS-275 decreases ethanol self-administration by about 75%. We found that 2 consecutive daily injections are necessary to decrease ethanol self-administration. Additionally, the dose-response curve test indicated that MS-275 has a...Continue Reading

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Citations

May 5, 2016·The American Journal of Drug and Alcohol Abuse·Ya-Hui XuRui-Ling Zhang
Mar 4, 2017·Neuropharmacology·Anna S Warden, R Dayne Mayfield
Jul 7, 2017·Biologie aujourd'hui·Rémi LegasteloisMickael Naassila
May 4, 2018·Expert Opinion on Investigational Drugs·Sarah S Ch'ng, Andrew J Lawrence
Jun 5, 2018·Addiction Biology·Jérôme JeanblancMickaël Naassila
Mar 3, 2020·Frontiers in Neuroscience·Asha Jacob, Ping Wang
May 31, 2017·Addiction Biology·Sophie LebourgeoisCatherine Vilpoux
May 2, 2018·Psychopharmacology·Jérôme JeanblancMickaël Naassila
Jan 24, 2017·Alcoholism, Clinical and Experimental Research·Tiffani D M Berkel, Subhash C Pandey
Oct 27, 2020·Frontiers in Cell and Developmental Biology·Ryan D Shepard, Fereshteh S Nugent
Feb 19, 2021·Pharmacological Reviews·Mariana Angoa-Pérez, Donald M Kuhn
May 9, 2018·Neuroscience and Biobehavioral Reviews·Jérôme JeanblancMickael Naassila
Aug 5, 2017·Journal of Medicinal Chemistry·Erika BourguetMickaël Naassila

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Methods Mentioned

BETA
histone acetylation
acetylation

Software Mentioned

Mercator

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