Association of time-dependent changes in mu opioid receptor mRNA, but not BDNF, TrkB, or MeCP2 mRNA and protein expression in the rat nucleus accumbens with incubation of heroin craving

Rationale and objectives Responding to heroin cues progressively increases after cessation of heroin self-administration (incubation of heroin craving). We investigated whether this incubation is associated with time-dependent changes in brain-derived neurotrophic factor (BDNF) and methyl-CpG bindin...

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Veröffentlicht in:Psychopharmacologia 2012-12, Vol.224 (4), p.559-571
Hauptverfasser: Theberge, Florence R. M., Pickens, Charles L., Goldart, Evan, Fanous, Sanya, Hope, Bruce T., Liu, Qing-Rong, Shaham, Yavin
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container_end_page 571
container_issue 4
container_start_page 559
container_title Psychopharmacologia
container_volume 224
creator Theberge, Florence R. M.
Pickens, Charles L.
Goldart, Evan
Fanous, Sanya
Hope, Bruce T.
Liu, Qing-Rong
Shaham, Yavin
description Rationale and objectives Responding to heroin cues progressively increases after cessation of heroin self-administration (incubation of heroin craving). We investigated whether this incubation is associated with time-dependent changes in brain-derived neurotrophic factor (BDNF) and methyl-CpG binding protein 2 (MeCP2) signaling and mu opioid receptor (MOR) expression in nucleus accumbens (NAc), dorsal striatum (DS), and medial prefrontal cortex (mPFC). We also investigated the effect of the preferential MOR antagonist naloxone on cue-induced heroin seeking during abstinence. Methods We trained rats to self-administer heroin or saline for 9–10 days and then dissected the NAc, DS, and mPFC at different abstinence days and measured mRNA and protein levels of BDNF, TrkB, and MeCP2, as well as MOR mRNA ( Oprm1 ). In other groups, we assessed cue-induced heroin seeking in extinction tests after 1, 11, and 30 abstinence days, and naloxone’s (0–1.0 mg/kg) effect on extinction responding after 1 and 15 days. Results Cue-induced heroin seeking progressively increased or incubated during abstinence. This incubation was not associated with changes in BDNF, TrkB, or MeCP2 mRNA or protein levels in NAc, DS, or mPFC; additionally, no molecular changes were observed after extinction tests on day 11. In NAc, but not DS or mPFC, MOR mRNA decreased on abstinence day 1 and returned to basal levels over time. Naloxone significantly decreased cue-induced heroin seeking after 15 abstinence days but not 1 day. Conclusions Results suggest a role of MOR in incubation of heroin craving. As previous studies implicated NAc BDNF in incubation of cocaine craving, our data suggest that different mechanisms contribute to incubation of heroin versus cocaine craving.
doi_str_mv 10.1007/s00213-012-2784-z
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M. ; Pickens, Charles L. ; Goldart, Evan ; Fanous, Sanya ; Hope, Bruce T. ; Liu, Qing-Rong ; Shaham, Yavin</creator><creatorcontrib>Theberge, Florence R. M. ; Pickens, Charles L. ; Goldart, Evan ; Fanous, Sanya ; Hope, Bruce T. ; Liu, Qing-Rong ; Shaham, Yavin</creatorcontrib><description>Rationale and objectives Responding to heroin cues progressively increases after cessation of heroin self-administration (incubation of heroin craving). We investigated whether this incubation is associated with time-dependent changes in brain-derived neurotrophic factor (BDNF) and methyl-CpG binding protein 2 (MeCP2) signaling and mu opioid receptor (MOR) expression in nucleus accumbens (NAc), dorsal striatum (DS), and medial prefrontal cortex (mPFC). We also investigated the effect of the preferential MOR antagonist naloxone on cue-induced heroin seeking during abstinence. Methods We trained rats to self-administer heroin or saline for 9–10 days and then dissected the NAc, DS, and mPFC at different abstinence days and measured mRNA and protein levels of BDNF, TrkB, and MeCP2, as well as MOR mRNA ( Oprm1 ). In other groups, we assessed cue-induced heroin seeking in extinction tests after 1, 11, and 30 abstinence days, and naloxone’s (0–1.0 mg/kg) effect on extinction responding after 1 and 15 days. Results Cue-induced heroin seeking progressively increased or incubated during abstinence. This incubation was not associated with changes in BDNF, TrkB, or MeCP2 mRNA or protein levels in NAc, DS, or mPFC; additionally, no molecular changes were observed after extinction tests on day 11. In NAc, but not DS or mPFC, MOR mRNA decreased on abstinence day 1 and returned to basal levels over time. Naloxone significantly decreased cue-induced heroin seeking after 15 abstinence days but not 1 day. Conclusions Results suggest a role of MOR in incubation of heroin craving. As previous studies implicated NAc BDNF in incubation of cocaine craving, our data suggest that different mechanisms contribute to incubation of heroin versus cocaine craving.</description><identifier>ISSN: 0033-3158</identifier><identifier>EISSN: 1432-2072</identifier><identifier>DOI: 10.1007/s00213-012-2784-z</identifier><identifier>PMID: 22790874</identifier><identifier>CODEN: PSYPAG</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>Animals ; Behavioral decision theory ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Brain-Derived Neurotrophic Factor ; Cocaine ; Cues ; Dose-Response Relationship, Drug ; Drug addiction ; Gene Expression Regulation - drug effects ; Heroin ; Heroin - administration &amp; dosage ; Heroin Dependence - psychology ; Male ; Medical sciences ; Messenger RNA ; Methyl-CpG-Binding Protein 2 - genetics ; Naloxone - administration &amp; dosage ; Naloxone - pharmacology ; Narcotic Antagonists - administration &amp; dosage ; Narcotic Antagonists - pharmacology ; Neurosciences ; Nucleus Accumbens - drug effects ; Nucleus Accumbens - metabolism ; Original Investigation ; Pharmacology/Toxicology ; Protein binding ; Psychiatry ; Psychopharmacology ; Rats ; Rats, Sprague-Dawley ; Receptor, trkB - genetics ; Receptors, Opioid, mu - genetics ; RNA, Messenger - metabolism ; Self Administration ; Time Factors</subject><ispartof>Psychopharmacologia, 2012-12, Vol.224 (4), p.559-571</ispartof><rights>Springer-Verlag (outside the USA) 2012</rights><rights>2014 INIST-CNRS</rights><rights>COPYRIGHT 2012 Springer</rights><rights>Springer-Verlag Berlin Heidelberg 2012</rights><rights>Springer-Verlag (outside the USA) 2012 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c600t-e40acaff047fe33d4f3b1ff54bc243dcea72122a5ded2f990a3e389fbb2ebe513</citedby><cites>FETCH-LOGICAL-c600t-e40acaff047fe33d4f3b1ff54bc243dcea72122a5ded2f990a3e389fbb2ebe513</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00213-012-2784-z$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00213-012-2784-z$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=26640586$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22790874$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Theberge, Florence R. M.</creatorcontrib><creatorcontrib>Pickens, Charles L.</creatorcontrib><creatorcontrib>Goldart, Evan</creatorcontrib><creatorcontrib>Fanous, Sanya</creatorcontrib><creatorcontrib>Hope, Bruce T.</creatorcontrib><creatorcontrib>Liu, Qing-Rong</creatorcontrib><creatorcontrib>Shaham, Yavin</creatorcontrib><title>Association of time-dependent changes in mu opioid receptor mRNA, but not BDNF, TrkB, or MeCP2 mRNA and protein expression in the rat nucleus accumbens with incubation of heroin craving</title><title>Psychopharmacologia</title><addtitle>Psychopharmacology</addtitle><addtitle>Psychopharmacology (Berl)</addtitle><description>Rationale and objectives Responding to heroin cues progressively increases after cessation of heroin self-administration (incubation of heroin craving). We investigated whether this incubation is associated with time-dependent changes in brain-derived neurotrophic factor (BDNF) and methyl-CpG binding protein 2 (MeCP2) signaling and mu opioid receptor (MOR) expression in nucleus accumbens (NAc), dorsal striatum (DS), and medial prefrontal cortex (mPFC). We also investigated the effect of the preferential MOR antagonist naloxone on cue-induced heroin seeking during abstinence. Methods We trained rats to self-administer heroin or saline for 9–10 days and then dissected the NAc, DS, and mPFC at different abstinence days and measured mRNA and protein levels of BDNF, TrkB, and MeCP2, as well as MOR mRNA ( Oprm1 ). In other groups, we assessed cue-induced heroin seeking in extinction tests after 1, 11, and 30 abstinence days, and naloxone’s (0–1.0 mg/kg) effect on extinction responding after 1 and 15 days. Results Cue-induced heroin seeking progressively increased or incubated during abstinence. This incubation was not associated with changes in BDNF, TrkB, or MeCP2 mRNA or protein levels in NAc, DS, or mPFC; additionally, no molecular changes were observed after extinction tests on day 11. In NAc, but not DS or mPFC, MOR mRNA decreased on abstinence day 1 and returned to basal levels over time. Naloxone significantly decreased cue-induced heroin seeking after 15 abstinence days but not 1 day. Conclusions Results suggest a role of MOR in incubation of heroin craving. As previous studies implicated NAc BDNF in incubation of cocaine craving, our data suggest that different mechanisms contribute to incubation of heroin versus cocaine craving.</description><subject>Animals</subject><subject>Behavioral decision theory</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Brain-Derived Neurotrophic Factor</subject><subject>Cocaine</subject><subject>Cues</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug addiction</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Heroin</subject><subject>Heroin - administration &amp; dosage</subject><subject>Heroin Dependence - psychology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Messenger RNA</subject><subject>Methyl-CpG-Binding Protein 2 - genetics</subject><subject>Naloxone - administration &amp; dosage</subject><subject>Naloxone - pharmacology</subject><subject>Narcotic Antagonists - administration &amp; dosage</subject><subject>Narcotic Antagonists - pharmacology</subject><subject>Neurosciences</subject><subject>Nucleus Accumbens - drug effects</subject><subject>Nucleus Accumbens - metabolism</subject><subject>Original Investigation</subject><subject>Pharmacology/Toxicology</subject><subject>Protein binding</subject><subject>Psychiatry</subject><subject>Psychopharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptor, trkB - genetics</subject><subject>Receptors, Opioid, mu - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Self Administration</subject><subject>Time Factors</subject><issn>0033-3158</issn><issn>1432-2072</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kt9u0zAUxiMEYmXwANwgSwiJi2b4X-r0BqkrDJDGQGhcW45z3HokdrCdAXsz3g6Xlm5D4FxYJ-f3fScn-oriMcFHBGPxImJMCSsxoSUVNS-v7hQTwlmusKB3iwnGjJWMVPVB8SDGC5wPr_n94oBSMce14JPi5yJGr61K1jvkDUq2h7KFAVwLLiG9Vm4FEVmH-hH5wXrbogAahuQD6j-dLaaoGRNyPqHjV2cnU3QevhxPUW6-h-VH-htByrVoCD5BtoHvQ4AYN-NyldaAgsr6UXcwRqS0HvsGXETfbFpnQo_N_tvWEHzW6KAurVs9LO4Z1UV4tLsPi88nr8-Xb8vTD2_eLRenpZ5hnErgWGllDObCAGMtN6whxlS80ZSzVoMSlFCqqhZaauZzrBiwem6ahkIDFWGHxcut7zA2PWSBS0F1cgi2V-GH9MrK2x1n13LlLyWr5gzzjcHznUHwX0eISfY2aug65cCPURJaCSEI4TyjT_9CL_wYXF5PEjIXpCaMVdfUSnUgrTM-z9UbU7lgFSd8xqjI1NE_qPy00FvtHRib398SkK1ABx9jALPfkWC5yZvc5k3mvMlN3uRV1jy5-XP2ij8By8CzHaCiVp0Jymkbr7nZjOOqnmWObrmYWzly4cbm_53-Cy0J738</recordid><startdate>20121201</startdate><enddate>20121201</enddate><creator>Theberge, Florence R. 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M.</creatorcontrib><creatorcontrib>Pickens, Charles L.</creatorcontrib><creatorcontrib>Goldart, Evan</creatorcontrib><creatorcontrib>Fanous, Sanya</creatorcontrib><creatorcontrib>Hope, Bruce T.</creatorcontrib><creatorcontrib>Liu, Qing-Rong</creatorcontrib><creatorcontrib>Shaham, Yavin</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>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Nursing &amp; Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health &amp; 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>Technology Research Database</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>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</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>Nucleic Acids Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Psychopharmacologia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Theberge, Florence R. M.</au><au>Pickens, Charles L.</au><au>Goldart, Evan</au><au>Fanous, Sanya</au><au>Hope, Bruce T.</au><au>Liu, Qing-Rong</au><au>Shaham, Yavin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of time-dependent changes in mu opioid receptor mRNA, but not BDNF, TrkB, or MeCP2 mRNA and protein expression in the rat nucleus accumbens with incubation of heroin craving</atitle><jtitle>Psychopharmacologia</jtitle><stitle>Psychopharmacology</stitle><addtitle>Psychopharmacology (Berl)</addtitle><date>2012-12-01</date><risdate>2012</risdate><volume>224</volume><issue>4</issue><spage>559</spage><epage>571</epage><pages>559-571</pages><issn>0033-3158</issn><eissn>1432-2072</eissn><coden>PSYPAG</coden><abstract>Rationale and objectives Responding to heroin cues progressively increases after cessation of heroin self-administration (incubation of heroin craving). We investigated whether this incubation is associated with time-dependent changes in brain-derived neurotrophic factor (BDNF) and methyl-CpG binding protein 2 (MeCP2) signaling and mu opioid receptor (MOR) expression in nucleus accumbens (NAc), dorsal striatum (DS), and medial prefrontal cortex (mPFC). We also investigated the effect of the preferential MOR antagonist naloxone on cue-induced heroin seeking during abstinence. Methods We trained rats to self-administer heroin or saline for 9–10 days and then dissected the NAc, DS, and mPFC at different abstinence days and measured mRNA and protein levels of BDNF, TrkB, and MeCP2, as well as MOR mRNA ( Oprm1 ). In other groups, we assessed cue-induced heroin seeking in extinction tests after 1, 11, and 30 abstinence days, and naloxone’s (0–1.0 mg/kg) effect on extinction responding after 1 and 15 days. Results Cue-induced heroin seeking progressively increased or incubated during abstinence. This incubation was not associated with changes in BDNF, TrkB, or MeCP2 mRNA or protein levels in NAc, DS, or mPFC; additionally, no molecular changes were observed after extinction tests on day 11. In NAc, but not DS or mPFC, MOR mRNA decreased on abstinence day 1 and returned to basal levels over time. Naloxone significantly decreased cue-induced heroin seeking after 15 abstinence days but not 1 day. Conclusions Results suggest a role of MOR in incubation of heroin craving. As previous studies implicated NAc BDNF in incubation of cocaine craving, our data suggest that different mechanisms contribute to incubation of heroin versus cocaine craving.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>22790874</pmid><doi>10.1007/s00213-012-2784-z</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record>
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subjects Animals
Behavioral decision theory
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Brain-Derived Neurotrophic Factor
Cocaine
Cues
Dose-Response Relationship, Drug
Drug addiction
Gene Expression Regulation - drug effects
Heroin
Heroin - administration & dosage
Heroin Dependence - psychology
Male
Medical sciences
Messenger RNA
Methyl-CpG-Binding Protein 2 - genetics
Naloxone - administration & dosage
Naloxone - pharmacology
Narcotic Antagonists - administration & dosage
Narcotic Antagonists - pharmacology
Neurosciences
Nucleus Accumbens - drug effects
Nucleus Accumbens - metabolism
Original Investigation
Pharmacology/Toxicology
Protein binding
Psychiatry
Psychopharmacology
Rats
Rats, Sprague-Dawley
Receptor, trkB - genetics
Receptors, Opioid, mu - genetics
RNA, Messenger - metabolism
Self Administration
Time Factors
title Association of time-dependent changes in mu opioid receptor mRNA, but not BDNF, TrkB, or MeCP2 mRNA and protein expression in the rat nucleus accumbens with incubation of heroin craving
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