Dorsal Hippocampus Drives Context-Induced Cocaine Seeking via Inputs to Lateral Septum
Lateral septum (LS) has re-emerged as an important structure in reward and addiction; however, LS afferents that drive addiction behaviors are unknown. Here, we used a modified self-administration/reinstatement procedure combined with anatomical, pharmacological, and chemogenetic techniques to chara...
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| Veröffentlicht in: | Neuropsychopharmacology (New York, N.Y.) N.Y.), 2018-04, Vol.43 (5), p.987-1000 |
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| creator | McGlinchey, Ellen M Aston-Jones, Gary |
| description | Lateral septum (LS) has re-emerged as an important structure in reward and addiction; however, LS afferents that drive addiction behaviors are unknown. Here, we used a modified self-administration/reinstatement procedure combined with anatomical, pharmacological, and chemogenetic techniques to characterize LS, and hippocampal inputs to LS, in two established triggers of drug relapse-context- and cue-induced reinstatement of cocaine seeking. We found that inactivation of LS neurons attenuated both context- and cue-induced reinstatement of cocaine seeking. However, dorsal hippocampus inputs to LS showed enhanced neuronal activation (as measured by Fos expression) during context-induced, but not cue-induced reinstatement. Additionally, chemogenetic inhibition of dorsal, but not ventral, hippocampal inputs to LS specifically attenuated context-induced reinstatement. Together these findings elucidate the importance of LS in reinstatement of cocaine seeking, and indicate that dorsal hippocampal inputs to LS mediate context-, but not cue-induced, reinstatement of cocaine seeking. |
| doi_str_mv | 10.1038/npp.2017.144 |
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Here, we used a modified self-administration/reinstatement procedure combined with anatomical, pharmacological, and chemogenetic techniques to characterize LS, and hippocampal inputs to LS, in two established triggers of drug relapse-context- and cue-induced reinstatement of cocaine seeking. We found that inactivation of LS neurons attenuated both context- and cue-induced reinstatement of cocaine seeking. However, dorsal hippocampus inputs to LS showed enhanced neuronal activation (as measured by Fos expression) during context-induced, but not cue-induced reinstatement. Additionally, chemogenetic inhibition of dorsal, but not ventral, hippocampal inputs to LS specifically attenuated context-induced reinstatement. Together these findings elucidate the importance of LS in reinstatement of cocaine seeking, and indicate that dorsal hippocampal inputs to LS mediate context-, but not cue-induced, reinstatement of cocaine seeking.</description><identifier>ISSN: 0893-133X</identifier><identifier>EISSN: 1740-634X</identifier><identifier>DOI: 10.1038/npp.2017.144</identifier><identifier>PMID: 28695893</identifier><language>eng</language><publisher>England: Nature Publishing Group</publisher><subject>Addictions ; Animals ; Baclofen - pharmacology ; Behavior, Addictive ; Clozapine - analogs & derivatives ; Clozapine - pharmacology ; Cocaine ; Cocaine - pharmacology ; Cues ; Drug abuse ; Drug self-administration ; Drug-Seeking Behavior - drug effects ; Drug-Seeking Behavior - physiology ; Extinction, Psychological - drug effects ; Hippocampus ; Hippocampus - drug effects ; Hippocampus - physiology ; Inactivation ; Locomotion - drug effects ; Male ; Microinjections ; Muscimol - pharmacology ; Narcotics ; Neuroanatomical Tract-Tracing Techniques ; Oncogene Proteins v-fos - metabolism ; Original ; Rats ; Reinforcement ; Reinstatement ; Self Administration ; Septal Nuclei - drug effects ; Septal Nuclei - physiology ; Septum</subject><ispartof>Neuropsychopharmacology (New York, N.Y.), 2018-04, Vol.43 (5), p.987-1000</ispartof><rights>Copyright Nature Publishing Group Apr 2018</rights><rights>Copyright © 2018 American College of Neuropsychopharmacology 2018 American College of Neuropsychopharmacology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-fa44c26ae85b14590a7edf2a124f9fce258a3e0d0b73474d584ab21dedbe8be13</citedby><cites>FETCH-LOGICAL-c478t-fa44c26ae85b14590a7edf2a124f9fce258a3e0d0b73474d584ab21dedbe8be13</cites><orcidid>0000-0001-6322-4165</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5854789/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5854789/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28695893$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>McGlinchey, Ellen M</creatorcontrib><creatorcontrib>Aston-Jones, Gary</creatorcontrib><title>Dorsal Hippocampus Drives Context-Induced Cocaine Seeking via Inputs to Lateral Septum</title><title>Neuropsychopharmacology (New York, N.Y.)</title><addtitle>Neuropsychopharmacology</addtitle><description>Lateral septum (LS) has re-emerged as an important structure in reward and addiction; however, LS afferents that drive addiction behaviors are unknown. Here, we used a modified self-administration/reinstatement procedure combined with anatomical, pharmacological, and chemogenetic techniques to characterize LS, and hippocampal inputs to LS, in two established triggers of drug relapse-context- and cue-induced reinstatement of cocaine seeking. We found that inactivation of LS neurons attenuated both context- and cue-induced reinstatement of cocaine seeking. However, dorsal hippocampus inputs to LS showed enhanced neuronal activation (as measured by Fos expression) during context-induced, but not cue-induced reinstatement. Additionally, chemogenetic inhibition of dorsal, but not ventral, hippocampal inputs to LS specifically attenuated context-induced reinstatement. Together these findings elucidate the importance of LS in reinstatement of cocaine seeking, and indicate that dorsal hippocampal inputs to LS mediate context-, but not cue-induced, reinstatement of cocaine seeking.</description><subject>Addictions</subject><subject>Animals</subject><subject>Baclofen - pharmacology</subject><subject>Behavior, Addictive</subject><subject>Clozapine - analogs & derivatives</subject><subject>Clozapine - pharmacology</subject><subject>Cocaine</subject><subject>Cocaine - pharmacology</subject><subject>Cues</subject><subject>Drug abuse</subject><subject>Drug self-administration</subject><subject>Drug-Seeking Behavior - drug effects</subject><subject>Drug-Seeking Behavior - physiology</subject><subject>Extinction, Psychological - drug effects</subject><subject>Hippocampus</subject><subject>Hippocampus - drug effects</subject><subject>Hippocampus - physiology</subject><subject>Inactivation</subject><subject>Locomotion - drug effects</subject><subject>Male</subject><subject>Microinjections</subject><subject>Muscimol - pharmacology</subject><subject>Narcotics</subject><subject>Neuroanatomical Tract-Tracing Techniques</subject><subject>Oncogene Proteins v-fos - metabolism</subject><subject>Original</subject><subject>Rats</subject><subject>Reinforcement</subject><subject>Reinstatement</subject><subject>Self Administration</subject><subject>Septal Nuclei - drug effects</subject><subject>Septal Nuclei - physiology</subject><subject>Septum</subject><issn>0893-133X</issn><issn>1740-634X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpdkc1v1DAQxS1ERZfCjTOKxIUDWfwZOxcktAW60kocCqg3y3EmxWVjG9tZ0f8eV_1Q4TQazW-e3sxD6BXBa4KZeu9jXFNM5Jpw_gStiOS47Ri_eIpWWPWsJYxdHKPnOV9hTITs1DN0TFXXizpcoR-nIWWzb85cjMGaOS65OU3uALnZBF_gT2m3flwsjLW3xnlozgF-OX_ZHJxptj4uJTclNDtTIFWhc4hlmV-go8nsM7y8qyfo--dP3zZn7e7rl-3m4661XKrSToZzSzsDSgyEix4bCeNEDaF86icLVCjDAI94kIxLPgrFzUDJCOMAagDCTtCHW924DDOMFnypJnRMbjbpWgfj9L8T737qy3DQQonqoK8Cb-8EUvi9QC56dtnCfm88hCVr0hPZd0QoVtE3_6FXYUm-nqfr_1lHq0VaqXe3lE0h5wTTgxmC9U1gugZ2syB1Dazirx8f8ADfJ8T-AgYqkyE</recordid><startdate>20180401</startdate><enddate>20180401</enddate><creator>McGlinchey, Ellen M</creator><creator>Aston-Jones, Gary</creator><general>Nature Publishing Group</general><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>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6322-4165</orcidid></search><sort><creationdate>20180401</creationdate><title>Dorsal Hippocampus Drives Context-Induced Cocaine Seeking via Inputs to Lateral Septum</title><author>McGlinchey, Ellen M ; Aston-Jones, Gary</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c478t-fa44c26ae85b14590a7edf2a124f9fce258a3e0d0b73474d584ab21dedbe8be13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Addictions</topic><topic>Animals</topic><topic>Baclofen - pharmacology</topic><topic>Behavior, Addictive</topic><topic>Clozapine - analogs & derivatives</topic><topic>Clozapine - pharmacology</topic><topic>Cocaine</topic><topic>Cocaine - pharmacology</topic><topic>Cues</topic><topic>Drug abuse</topic><topic>Drug self-administration</topic><topic>Drug-Seeking Behavior - drug effects</topic><topic>Drug-Seeking Behavior - physiology</topic><topic>Extinction, Psychological - drug effects</topic><topic>Hippocampus</topic><topic>Hippocampus - drug effects</topic><topic>Hippocampus - physiology</topic><topic>Inactivation</topic><topic>Locomotion - drug effects</topic><topic>Male</topic><topic>Microinjections</topic><topic>Muscimol - pharmacology</topic><topic>Narcotics</topic><topic>Neuroanatomical Tract-Tracing Techniques</topic><topic>Oncogene Proteins v-fos - metabolism</topic><topic>Original</topic><topic>Rats</topic><topic>Reinforcement</topic><topic>Reinstatement</topic><topic>Self Administration</topic><topic>Septal Nuclei - drug effects</topic><topic>Septal Nuclei - physiology</topic><topic>Septum</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>McGlinchey, Ellen M</creatorcontrib><creatorcontrib>Aston-Jones, Gary</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Neuropsychopharmacology (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>McGlinchey, Ellen M</au><au>Aston-Jones, Gary</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dorsal Hippocampus Drives Context-Induced Cocaine Seeking via Inputs to Lateral Septum</atitle><jtitle>Neuropsychopharmacology (New York, N.Y.)</jtitle><addtitle>Neuropsychopharmacology</addtitle><date>2018-04-01</date><risdate>2018</risdate><volume>43</volume><issue>5</issue><spage>987</spage><epage>1000</epage><pages>987-1000</pages><issn>0893-133X</issn><eissn>1740-634X</eissn><abstract>Lateral septum (LS) has re-emerged as an important structure in reward and addiction; however, LS afferents that drive addiction behaviors are unknown. Here, we used a modified self-administration/reinstatement procedure combined with anatomical, pharmacological, and chemogenetic techniques to characterize LS, and hippocampal inputs to LS, in two established triggers of drug relapse-context- and cue-induced reinstatement of cocaine seeking. We found that inactivation of LS neurons attenuated both context- and cue-induced reinstatement of cocaine seeking. However, dorsal hippocampus inputs to LS showed enhanced neuronal activation (as measured by Fos expression) during context-induced, but not cue-induced reinstatement. Additionally, chemogenetic inhibition of dorsal, but not ventral, hippocampal inputs to LS specifically attenuated context-induced reinstatement. Together these findings elucidate the importance of LS in reinstatement of cocaine seeking, and indicate that dorsal hippocampal inputs to LS mediate context-, but not cue-induced, reinstatement of cocaine seeking.</abstract><cop>England</cop><pub>Nature Publishing Group</pub><pmid>28695893</pmid><doi>10.1038/npp.2017.144</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0001-6322-4165</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Addictions Animals Baclofen - pharmacology Behavior, Addictive Clozapine - analogs & derivatives Clozapine - pharmacology Cocaine Cocaine - pharmacology Cues Drug abuse Drug self-administration Drug-Seeking Behavior - drug effects Drug-Seeking Behavior - physiology Extinction, Psychological - drug effects Hippocampus Hippocampus - drug effects Hippocampus - physiology Inactivation Locomotion - drug effects Male Microinjections Muscimol - pharmacology Narcotics Neuroanatomical Tract-Tracing Techniques Oncogene Proteins v-fos - metabolism Original Rats Reinforcement Reinstatement Self Administration Septal Nuclei - drug effects Septal Nuclei - physiology Septum |
| title | Dorsal Hippocampus Drives Context-Induced Cocaine Seeking via Inputs to Lateral Septum |
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