Interest of new alkylsulfonylhydrazide-type compound in the treatment of alcohol use disorders
Rationale Recent preclinical research suggested that histone deacetylase inhibitors (HDACIs) and specifically class I HDAC selective inhibitors might be useful to treat alcohol use disorders (AUDs). Objective The objective of this study was to find a new inhibitor of the HDAC-1 isoenzyme and to test...
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| Veröffentlicht in: | Psychopharmacology 2018-06, Vol.235 (6), p.1835-1844 |
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| creator | Jeanblanc, Jérôme Bourguet, Erika Sketriené, Diana Gonzalez, Céline Moroy, Gautier Legastelois, Rémi Létévé, Mathieu Trussardi-Régnier, Aurélie Naassila, Mickaël |
| description | Rationale
Recent preclinical research suggested that histone deacetylase inhibitors (HDACIs) and specifically class I HDAC selective inhibitors might be useful to treat alcohol use disorders (AUDs).
Objective
The objective of this study was to find a new inhibitor of the HDAC-1 isoenzyme and to test its efficacy in an animal model of AUDs.
Methods
In the present study, we prepared new derivatives bearing sulfonylhydrazide-type zinc-binding group (ZBG) and evaluated these compounds in vitro on HDAC-1 isoenzyme. The most promising compound was tested on ethanol operant self-administration and relapse in rats.
Results
We showed that the alkylsulfonylhydrazide-type compound (ASH) reduced by more than 55% the total amount of ethanol consumed after one intracerebroventricular microinjection, while no effect was observed on motivation of the animals to consume ethanol. In addition, one ASH injection in the central amygdala reduced relapse.
Conclusions
Our study demonstrated that a new compound designed to target HDAC-1 is effective in reducing ethanol intake and relapse in rats and further confirm the interest of pursuing research to study the exact mechanism by which such inhibitor may be useful to treat AUDs. |
| doi_str_mv | 10.1007/s00213-018-4917-5 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_hal_01929565v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A538440506</galeid><sourcerecordid>A538440506</sourcerecordid><originalsourceid>FETCH-LOGICAL-c386t-ba6382d1696097ba9409cc0df1931ed201f00e590a5b3a36f5e27470ae64b34a3</originalsourceid><addsrcrecordid>eNp1kU9v1DAQxS0EokvhA3BBkbjAITD-m_i4qoBWWokLXLGcZNJNcezFTorCp8chpZWQ8GUk-zfPb-YR8pLCOwpQvU8AjPISaF0KTatSPiI7KjgrGVTsMdkBcF5yKusz8iylG8hH1OIpOWO6oryq1Y58u_ITRkxTEfrC48_Cuu-LS7Prg1_ccemi_TV0WE7LCYs2jKcw-64YfDEdsZgi2mlE_6fZujYcgyvmhEU3pBA7jOk5edJbl_DFXT0nXz9--HJxWR4-f7q62B_KltdqKhureM06qrQCXTVWC9BtC11PNafYMaA9AEoNVjbcctVLZJWowKISDReWn5O3m-7ROnOKw2jjYoIdzOX-YNY7oJppqeQtzeybjT3F8GPOo5txSC06Zz2GORmWt5Zd1WxFX_-D3oQ5-jzJSrFsWoF8oK6tQzP4PkzRtquo2UteCwESVKboRrUxpBSxv_dJwaxxmi3ObLU2a5xmVX519__cjNjdd_zNLwNsA1J-8tcYHwz-X_U3JiGoXw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2032638605</pqid></control><display><type>article</type><title>Interest of new alkylsulfonylhydrazide-type compound in the treatment of alcohol use disorders</title><source>Springer Nature - Complete Springer Journals</source><creator>Jeanblanc, Jérôme ; Bourguet, Erika ; Sketriené, Diana ; Gonzalez, Céline ; Moroy, Gautier ; Legastelois, Rémi ; Létévé, Mathieu ; Trussardi-Régnier, Aurélie ; Naassila, Mickaël</creator><creatorcontrib>Jeanblanc, Jérôme ; Bourguet, Erika ; Sketriené, Diana ; Gonzalez, Céline ; Moroy, Gautier ; Legastelois, Rémi ; Létévé, Mathieu ; Trussardi-Régnier, Aurélie ; Naassila, Mickaël</creatorcontrib><description>Rationale
Recent preclinical research suggested that histone deacetylase inhibitors (HDACIs) and specifically class I HDAC selective inhibitors might be useful to treat alcohol use disorders (AUDs).
Objective
The objective of this study was to find a new inhibitor of the HDAC-1 isoenzyme and to test its efficacy in an animal model of AUDs.
Methods
In the present study, we prepared new derivatives bearing sulfonylhydrazide-type zinc-binding group (ZBG) and evaluated these compounds in vitro on HDAC-1 isoenzyme. The most promising compound was tested on ethanol operant self-administration and relapse in rats.
Results
We showed that the alkylsulfonylhydrazide-type compound (ASH) reduced by more than 55% the total amount of ethanol consumed after one intracerebroventricular microinjection, while no effect was observed on motivation of the animals to consume ethanol. In addition, one ASH injection in the central amygdala reduced relapse.
Conclusions
Our study demonstrated that a new compound designed to target HDAC-1 is effective in reducing ethanol intake and relapse in rats and further confirm the interest of pursuing research to study the exact mechanism by which such inhibitor may be useful to treat AUDs.</description><identifier>ISSN: 0033-3158</identifier><identifier>EISSN: 1432-2072</identifier><identifier>DOI: 10.1007/s00213-018-4917-5</identifier><identifier>PMID: 29713786</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Alcohol use ; Alcohol-related disorders ; Alcohols ; Amygdala ; Animal biology ; Ashes ; Biomedical and Life Sciences ; Biomedicine ; Care and treatment ; Chemical Sciences ; Cognitive science ; Drug self-administration ; Enzymes ; Ethanol ; Histone deacetylase ; Inhibitors ; Life Sciences ; Microinjection ; Motivation ; Neuroscience ; Neurosciences ; Operant conditioning ; Organic chemistry ; Organic compounds ; Original Investigation ; Pharmacology/Toxicology ; Physiological aspects ; Psychiatry ; Rats ; Sulfur compounds ; Zinc</subject><ispartof>Psychopharmacology, 2018-06, Vol.235 (6), p.1835-1844</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2018</rights><rights>COPYRIGHT 2018 Springer</rights><rights>Psychopharmacology is a copyright of Springer, (2018). All Rights Reserved.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c386t-ba6382d1696097ba9409cc0df1931ed201f00e590a5b3a36f5e27470ae64b34a3</cites><orcidid>0000-0002-9788-0918 ; 0000-0003-0353-2777 ; 0000-0002-1127-0546 ; 0000-0002-8973-0477 ; 0000-0003-3346-0372</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00213-018-4917-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00213-018-4917-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29713786$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-01929565$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Jeanblanc, Jérôme</creatorcontrib><creatorcontrib>Bourguet, Erika</creatorcontrib><creatorcontrib>Sketriené, Diana</creatorcontrib><creatorcontrib>Gonzalez, Céline</creatorcontrib><creatorcontrib>Moroy, Gautier</creatorcontrib><creatorcontrib>Legastelois, Rémi</creatorcontrib><creatorcontrib>Létévé, Mathieu</creatorcontrib><creatorcontrib>Trussardi-Régnier, Aurélie</creatorcontrib><creatorcontrib>Naassila, Mickaël</creatorcontrib><title>Interest of new alkylsulfonylhydrazide-type compound in the treatment of alcohol use disorders</title><title>Psychopharmacology</title><addtitle>Psychopharmacology</addtitle><addtitle>Psychopharmacology (Berl)</addtitle><description>Rationale
Recent preclinical research suggested that histone deacetylase inhibitors (HDACIs) and specifically class I HDAC selective inhibitors might be useful to treat alcohol use disorders (AUDs).
Objective
The objective of this study was to find a new inhibitor of the HDAC-1 isoenzyme and to test its efficacy in an animal model of AUDs.
Methods
In the present study, we prepared new derivatives bearing sulfonylhydrazide-type zinc-binding group (ZBG) and evaluated these compounds in vitro on HDAC-1 isoenzyme. The most promising compound was tested on ethanol operant self-administration and relapse in rats.
Results
We showed that the alkylsulfonylhydrazide-type compound (ASH) reduced by more than 55% the total amount of ethanol consumed after one intracerebroventricular microinjection, while no effect was observed on motivation of the animals to consume ethanol. In addition, one ASH injection in the central amygdala reduced relapse.
Conclusions
Our study demonstrated that a new compound designed to target HDAC-1 is effective in reducing ethanol intake and relapse in rats and further confirm the interest of pursuing research to study the exact mechanism by which such inhibitor may be useful to treat AUDs.</description><subject>Alcohol use</subject><subject>Alcohol-related disorders</subject><subject>Alcohols</subject><subject>Amygdala</subject><subject>Animal biology</subject><subject>Ashes</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Care and treatment</subject><subject>Chemical Sciences</subject><subject>Cognitive science</subject><subject>Drug self-administration</subject><subject>Enzymes</subject><subject>Ethanol</subject><subject>Histone deacetylase</subject><subject>Inhibitors</subject><subject>Life Sciences</subject><subject>Microinjection</subject><subject>Motivation</subject><subject>Neuroscience</subject><subject>Neurosciences</subject><subject>Operant conditioning</subject><subject>Organic chemistry</subject><subject>Organic compounds</subject><subject>Original Investigation</subject><subject>Pharmacology/Toxicology</subject><subject>Physiological aspects</subject><subject>Psychiatry</subject><subject>Rats</subject><subject>Sulfur 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deacetylase</topic><topic>Inhibitors</topic><topic>Life Sciences</topic><topic>Microinjection</topic><topic>Motivation</topic><topic>Neuroscience</topic><topic>Neurosciences</topic><topic>Operant conditioning</topic><topic>Organic chemistry</topic><topic>Organic compounds</topic><topic>Original Investigation</topic><topic>Pharmacology/Toxicology</topic><topic>Physiological aspects</topic><topic>Psychiatry</topic><topic>Rats</topic><topic>Sulfur compounds</topic><topic>Zinc</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jeanblanc, Jérôme</creatorcontrib><creatorcontrib>Bourguet, Erika</creatorcontrib><creatorcontrib>Sketriené, Diana</creatorcontrib><creatorcontrib>Gonzalez, Céline</creatorcontrib><creatorcontrib>Moroy, Gautier</creatorcontrib><creatorcontrib>Legastelois, Rémi</creatorcontrib><creatorcontrib>Létévé, Mathieu</creatorcontrib><creatorcontrib>Trussardi-Régnier, Aurélie</creatorcontrib><creatorcontrib>Naassila, 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Mickaël</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interest of new alkylsulfonylhydrazide-type compound in the treatment of alcohol use disorders</atitle><jtitle>Psychopharmacology</jtitle><stitle>Psychopharmacology</stitle><addtitle>Psychopharmacology (Berl)</addtitle><date>2018-06-01</date><risdate>2018</risdate><volume>235</volume><issue>6</issue><spage>1835</spage><epage>1844</epage><pages>1835-1844</pages><issn>0033-3158</issn><eissn>1432-2072</eissn><abstract>Rationale
Recent preclinical research suggested that histone deacetylase inhibitors (HDACIs) and specifically class I HDAC selective inhibitors might be useful to treat alcohol use disorders (AUDs).
Objective
The objective of this study was to find a new inhibitor of the HDAC-1 isoenzyme and to test its efficacy in an animal model of AUDs.
Methods
In the present study, we prepared new derivatives bearing sulfonylhydrazide-type zinc-binding group (ZBG) and evaluated these compounds in vitro on HDAC-1 isoenzyme. The most promising compound was tested on ethanol operant self-administration and relapse in rats.
Results
We showed that the alkylsulfonylhydrazide-type compound (ASH) reduced by more than 55% the total amount of ethanol consumed after one intracerebroventricular microinjection, while no effect was observed on motivation of the animals to consume ethanol. In addition, one ASH injection in the central amygdala reduced relapse.
Conclusions
Our study demonstrated that a new compound designed to target HDAC-1 is effective in reducing ethanol intake and relapse in rats and further confirm the interest of pursuing research to study the exact mechanism by which such inhibitor may be useful to treat AUDs.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>29713786</pmid><doi>10.1007/s00213-018-4917-5</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-9788-0918</orcidid><orcidid>https://orcid.org/0000-0003-0353-2777</orcidid><orcidid>https://orcid.org/0000-0002-1127-0546</orcidid><orcidid>https://orcid.org/0000-0002-8973-0477</orcidid><orcidid>https://orcid.org/0000-0003-3346-0372</orcidid></addata></record> |
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| ispartof | Psychopharmacology, 2018-06, Vol.235 (6), p.1835-1844 |
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| source | Springer Nature - Complete Springer Journals |
| subjects | Alcohol use Alcohol-related disorders Alcohols Amygdala Animal biology Ashes Biomedical and Life Sciences Biomedicine Care and treatment Chemical Sciences Cognitive science Drug self-administration Enzymes Ethanol Histone deacetylase Inhibitors Life Sciences Microinjection Motivation Neuroscience Neurosciences Operant conditioning Organic chemistry Organic compounds Original Investigation Pharmacology/Toxicology Physiological aspects Psychiatry Rats Sulfur compounds Zinc |
| title | Interest of new alkylsulfonylhydrazide-type compound in the treatment of alcohol use disorders |
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