A selective ALDH-2 inhibitor reduces anxiety in rats
CVT-10216 is a highly selective, reversible inhibitor of ALDH-2 that reduces excessive alcohol drinking. Anxiety plays a role in alcoholism. The present study asks whether CVT-10216 has anxiolytic properties, as reflected in social interaction behavior in four unrelated rodent models: endogenous anx...
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| Veröffentlicht in: | Pharmacology, biochemistry and behavior biochemistry and behavior, 2009-12, Vol.94 (2), p.255-261 |
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| creator | Overstreet, David H. Knapp, Darin J. Breese, George R. Diamond, Ivan |
| description | CVT-10216 is a highly selective, reversible inhibitor of ALDH-2 that reduces excessive alcohol drinking. Anxiety plays a role in alcoholism. The present study asks whether CVT-10216 has anxiolytic properties, as reflected in social interaction behavior in four unrelated rodent models: endogenous anxiety-like behavior in naïve Fawn-Hooded rats, repeated alcohol-withdrawal-induced anxiety, restraint stress-induced anxiety and drug-induced anxiety. CVT-10216 counteracted anxiety in all models except that produced by the 5-HT
2C agonist, mCPP. CVT-10216 exhibited both acute and prophylactic inhibitions of repeated alcohol-withdrawal-induced anxiety. Importantly, anxiogenic behavior induced by the benzodiazepine receptor inverse agonist, DMCM, was counteracted dose-dependently by CVT-10216. Thus, a non-addictive selective inhibitor of ALDH-2 has both anxiolytic and antidipsotropic properties, which may be dependent, in part on the involvement of the GABA–benzodiazepine system. |
| doi_str_mv | 10.1016/j.pbb.2009.09.004 |
| format | Article |
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2C agonist, mCPP. CVT-10216 exhibited both acute and prophylactic inhibitions of repeated alcohol-withdrawal-induced anxiety. Importantly, anxiogenic behavior induced by the benzodiazepine receptor inverse agonist, DMCM, was counteracted dose-dependently by CVT-10216. Thus, a non-addictive selective inhibitor of ALDH-2 has both anxiolytic and antidipsotropic properties, which may be dependent, in part on the involvement of the GABA–benzodiazepine system.</description><identifier>ISSN: 0091-3057</identifier><identifier>EISSN: 1873-5177</identifier><identifier>DOI: 10.1016/j.pbb.2009.09.004</identifier><identifier>PMID: 19747934</identifier><identifier>CODEN: PBBHAU</identifier><language>eng</language><publisher>Kidlington: Elsevier Inc</publisher><subject>Alcohol Deterrents - chemistry ; Alcohol Deterrents - pharmacology ; Alcohol Deterrents - therapeutic use ; Aldehyde Dehydrogenase - antagonists & inhibitors ; Aldehyde Dehydrogenase - physiology ; Aldehyde Dehydrogenase, Mitochondrial ; ALDH-2 inhibitor ; Animals ; Anti-Anxiety Agents - chemistry ; Anti-Anxiety Agents - pharmacology ; Anti-Anxiety Agents - therapeutic use ; Anxiety - drug therapy ; Anxiety - psychology ; Anxiogenic behavior ; Biological and medical sciences ; DMCM ; Dose-Response Relationship, Drug ; Ethanol withdrawal ; Fawn-Hooded rats ; Isoflavones - chemistry ; Isoflavones - pharmacology ; Isoflavones - therapeutic use ; mCPP ; Medical sciences ; Mitochondrial Proteins - antagonists & inhibitors ; Mitochondrial Proteins - physiology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Restraint stress ; Social interaction test</subject><ispartof>Pharmacology, biochemistry and behavior, 2009-12, Vol.94 (2), p.255-261</ispartof><rights>2009 Elsevier Inc.</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c577t-d8b6a5527afa6017c62a1d018f671b85c736e8dc118cd83dbd06162fc02ce6923</citedby><cites>FETCH-LOGICAL-c577t-d8b6a5527afa6017c62a1d018f671b85c736e8dc118cd83dbd06162fc02ce6923</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0091305709002603$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27903,27904,65309</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22121179$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19747934$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Overstreet, David H.</creatorcontrib><creatorcontrib>Knapp, Darin J.</creatorcontrib><creatorcontrib>Breese, George R.</creatorcontrib><creatorcontrib>Diamond, Ivan</creatorcontrib><title>A selective ALDH-2 inhibitor reduces anxiety in rats</title><title>Pharmacology, biochemistry and behavior</title><addtitle>Pharmacol Biochem Behav</addtitle><description>CVT-10216 is a highly selective, reversible inhibitor of ALDH-2 that reduces excessive alcohol drinking. Anxiety plays a role in alcoholism. The present study asks whether CVT-10216 has anxiolytic properties, as reflected in social interaction behavior in four unrelated rodent models: endogenous anxiety-like behavior in naïve Fawn-Hooded rats, repeated alcohol-withdrawal-induced anxiety, restraint stress-induced anxiety and drug-induced anxiety. CVT-10216 counteracted anxiety in all models except that produced by the 5-HT
2C agonist, mCPP. CVT-10216 exhibited both acute and prophylactic inhibitions of repeated alcohol-withdrawal-induced anxiety. Importantly, anxiogenic behavior induced by the benzodiazepine receptor inverse agonist, DMCM, was counteracted dose-dependently by CVT-10216. Thus, a non-addictive selective inhibitor of ALDH-2 has both anxiolytic and antidipsotropic properties, which may be dependent, in part on the involvement of the GABA–benzodiazepine system.</description><subject>Alcohol Deterrents - chemistry</subject><subject>Alcohol Deterrents - pharmacology</subject><subject>Alcohol Deterrents - therapeutic use</subject><subject>Aldehyde Dehydrogenase - antagonists & inhibitors</subject><subject>Aldehyde Dehydrogenase - physiology</subject><subject>Aldehyde Dehydrogenase, Mitochondrial</subject><subject>ALDH-2 inhibitor</subject><subject>Animals</subject><subject>Anti-Anxiety Agents - chemistry</subject><subject>Anti-Anxiety Agents - pharmacology</subject><subject>Anti-Anxiety Agents - therapeutic use</subject><subject>Anxiety - drug therapy</subject><subject>Anxiety - psychology</subject><subject>Anxiogenic behavior</subject><subject>Biological and medical sciences</subject><subject>DMCM</subject><subject>Dose-Response Relationship, Drug</subject><subject>Ethanol withdrawal</subject><subject>Fawn-Hooded rats</subject><subject>Isoflavones - chemistry</subject><subject>Isoflavones - pharmacology</subject><subject>Isoflavones - therapeutic use</subject><subject>mCPP</subject><subject>Medical sciences</subject><subject>Mitochondrial Proteins - antagonists & inhibitors</subject><subject>Mitochondrial Proteins - physiology</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Restraint stress</subject><subject>Social interaction test</subject><issn>0091-3057</issn><issn>1873-5177</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kd9LwzAQx4Mobk7_AF-kL_rWmUvbpEUQhr8mDHzR55AmV5fRtTPphv73pmxMfREO8nCf-97xCSHnQMdAgV8vxquyHDNKi3FfND0gQ8hFEmcgxCEZhgbECc3EgJx4v6CBYFwckwEUIhVFkg5JOok81qg7u8FoMrufxiyyzdyWtmtd5NCsNfpINZ8Wu6_QiZzq_Ck5qlTt8Wz3jsjb48Pr3TSevTw9301msc6E6GKTl1xlGROqUpyC0JwpMBTyigso80yLhGNuNECuTZ6Y0lAOnFWaMo28YMmI3G5zV-tyiUZj0zlVy5WzS-W-ZKus_Ntp7Fy-txvJ8qwQ0Adc7QJc-7FG38ml9RrrWjXYrr1kABAciQDCFtSu9d5htV8CVPau5UIG17J3LfuiaZi5-H3dz8RObgAud4DyWtWVU422fs8xBmF_IEfkZsthcLmx6KTXFhuNxrrwM9K09p8zvgEH3puB</recordid><startdate>20091201</startdate><enddate>20091201</enddate><creator>Overstreet, David H.</creator><creator>Knapp, Darin J.</creator><creator>Breese, George R.</creator><creator>Diamond, Ivan</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7TK</scope><scope>5PM</scope></search><sort><creationdate>20091201</creationdate><title>A selective ALDH-2 inhibitor reduces anxiety in rats</title><author>Overstreet, David H. ; Knapp, Darin J. ; Breese, George R. ; Diamond, Ivan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c577t-d8b6a5527afa6017c62a1d018f671b85c736e8dc118cd83dbd06162fc02ce6923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Alcohol Deterrents - chemistry</topic><topic>Alcohol Deterrents - pharmacology</topic><topic>Alcohol Deterrents - therapeutic use</topic><topic>Aldehyde Dehydrogenase - antagonists & inhibitors</topic><topic>Aldehyde Dehydrogenase - physiology</topic><topic>Aldehyde Dehydrogenase, Mitochondrial</topic><topic>ALDH-2 inhibitor</topic><topic>Animals</topic><topic>Anti-Anxiety Agents - chemistry</topic><topic>Anti-Anxiety Agents - pharmacology</topic><topic>Anti-Anxiety Agents - therapeutic use</topic><topic>Anxiety - drug therapy</topic><topic>Anxiety - psychology</topic><topic>Anxiogenic behavior</topic><topic>Biological and medical sciences</topic><topic>DMCM</topic><topic>Dose-Response Relationship, Drug</topic><topic>Ethanol withdrawal</topic><topic>Fawn-Hooded rats</topic><topic>Isoflavones - chemistry</topic><topic>Isoflavones - pharmacology</topic><topic>Isoflavones - therapeutic use</topic><topic>mCPP</topic><topic>Medical sciences</topic><topic>Mitochondrial Proteins - antagonists & inhibitors</topic><topic>Mitochondrial Proteins - physiology</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Restraint stress</topic><topic>Social interaction test</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Overstreet, David H.</creatorcontrib><creatorcontrib>Knapp, Darin J.</creatorcontrib><creatorcontrib>Breese, George R.</creatorcontrib><creatorcontrib>Diamond, Ivan</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Pharmacology, biochemistry and behavior</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Overstreet, David H.</au><au>Knapp, Darin J.</au><au>Breese, George R.</au><au>Diamond, Ivan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A selective ALDH-2 inhibitor reduces anxiety in rats</atitle><jtitle>Pharmacology, biochemistry and behavior</jtitle><addtitle>Pharmacol Biochem Behav</addtitle><date>2009-12-01</date><risdate>2009</risdate><volume>94</volume><issue>2</issue><spage>255</spage><epage>261</epage><pages>255-261</pages><issn>0091-3057</issn><eissn>1873-5177</eissn><coden>PBBHAU</coden><abstract>CVT-10216 is a highly selective, reversible inhibitor of ALDH-2 that reduces excessive alcohol drinking. Anxiety plays a role in alcoholism. The present study asks whether CVT-10216 has anxiolytic properties, as reflected in social interaction behavior in four unrelated rodent models: endogenous anxiety-like behavior in naïve Fawn-Hooded rats, repeated alcohol-withdrawal-induced anxiety, restraint stress-induced anxiety and drug-induced anxiety. CVT-10216 counteracted anxiety in all models except that produced by the 5-HT
2C agonist, mCPP. CVT-10216 exhibited both acute and prophylactic inhibitions of repeated alcohol-withdrawal-induced anxiety. Importantly, anxiogenic behavior induced by the benzodiazepine receptor inverse agonist, DMCM, was counteracted dose-dependently by CVT-10216. Thus, a non-addictive selective inhibitor of ALDH-2 has both anxiolytic and antidipsotropic properties, which may be dependent, in part on the involvement of the GABA–benzodiazepine system.</abstract><cop>Kidlington</cop><pub>Elsevier Inc</pub><pmid>19747934</pmid><doi>10.1016/j.pbb.2009.09.004</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Alcohol Deterrents - chemistry Alcohol Deterrents - pharmacology Alcohol Deterrents - therapeutic use Aldehyde Dehydrogenase - antagonists & inhibitors Aldehyde Dehydrogenase - physiology Aldehyde Dehydrogenase, Mitochondrial ALDH-2 inhibitor Animals Anti-Anxiety Agents - chemistry Anti-Anxiety Agents - pharmacology Anti-Anxiety Agents - therapeutic use Anxiety - drug therapy Anxiety - psychology Anxiogenic behavior Biological and medical sciences DMCM Dose-Response Relationship, Drug Ethanol withdrawal Fawn-Hooded rats Isoflavones - chemistry Isoflavones - pharmacology Isoflavones - therapeutic use mCPP Medical sciences Mitochondrial Proteins - antagonists & inhibitors Mitochondrial Proteins - physiology Random Allocation Rats Rats, Sprague-Dawley Restraint stress Social interaction test |
| title | A selective ALDH-2 inhibitor reduces anxiety in rats |
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