Social Stress Engages Opioid Regulation of Locus Coeruleus Norepinephrine Neurons and Induces a State of Cellular and Physical Opiate Dependence
Stress is implicated in diverse psychiatric disorders including substance abuse. The locus coeruleus-norepinephrine (LC-NE) system is a major stress response system that is also a point of intersection between stress neuromediators and endogenous opioids and so may be a site at which stress can infl...
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| Veröffentlicht in: | Neuropsychopharmacology (New York, N.Y.) N.Y.), 2013-09, Vol.38 (10), p.1833-1843 |
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| creator | CHAIJALE, Nayla N CURTIS, Andre L WOOD, Susan K ZHANG, Xiao-Yan BHATNAGAR, Seema REYES, Beverly As VAN BOCKSTAELE, Elisabeth J VALENTINO, Rita J |
| description | Stress is implicated in diverse psychiatric disorders including substance abuse. The locus coeruleus-norepinephrine (LC-NE) system is a major stress response system that is also a point of intersection between stress neuromediators and endogenous opioids and so may be a site at which stress can influence drug-taking behaviors. As social stress is a common stressor for humans, this study characterized the enduring impact of repeated social stress on LC neuronal activity. Rats were exposed to five daily consecutive sessions of social stress using the resident-intruder model or control manipulation. LC discharge rate recorded 2 days after the last manipulation was decreased in stressed rats compared with controls. By 10 days after the last manipulation, LC rates were comparable between groups. Systemic administration of the opiate antagonist, naloxone, robustly increased LC discharge rate in a manner suggestive of opiate withdrawal, selectively in stressed rats when administered 2 or 10 days after the last manipulation. This was accompanied by behavioral signs of mild opiate withdrawal. Western blot and electron microscopic studies indicated that repeated social stress decreased corticotropin-releasing factor type 1 receptor and increased μ-opioid receptor levels in the LC. Together, the results suggest that repeated social stress engages endogenous opioid modulation of LC activity and induces signs of cellular and physical opiate dependence that endure after the stress. These cellular effects may predispose individuals with a history of repeated social stress to substance abuse behaviors. |
| doi_str_mv | 10.1038/npp.2013.117 |
| format | Article |
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The locus coeruleus-norepinephrine (LC-NE) system is a major stress response system that is also a point of intersection between stress neuromediators and endogenous opioids and so may be a site at which stress can influence drug-taking behaviors. As social stress is a common stressor for humans, this study characterized the enduring impact of repeated social stress on LC neuronal activity. Rats were exposed to five daily consecutive sessions of social stress using the resident-intruder model or control manipulation. LC discharge rate recorded 2 days after the last manipulation was decreased in stressed rats compared with controls. By 10 days after the last manipulation, LC rates were comparable between groups. Systemic administration of the opiate antagonist, naloxone, robustly increased LC discharge rate in a manner suggestive of opiate withdrawal, selectively in stressed rats when administered 2 or 10 days after the last manipulation. This was accompanied by behavioral signs of mild opiate withdrawal. Western blot and electron microscopic studies indicated that repeated social stress decreased corticotropin-releasing factor type 1 receptor and increased μ-opioid receptor levels in the LC. Together, the results suggest that repeated social stress engages endogenous opioid modulation of LC activity and induces signs of cellular and physical opiate dependence that endure after the stress. These cellular effects may predispose individuals with a history of repeated social stress to substance abuse behaviors.</description><identifier>ISSN: 0893-133X</identifier><identifier>EISSN: 1740-634X</identifier><identifier>DOI: 10.1038/npp.2013.117</identifier><identifier>PMID: 23660707</identifier><identifier>CODEN: NEROEW</identifier><language>eng</language><publisher>Basingstoke: Nature Publishing Group</publisher><subject>Action Potentials - drug effects ; Action Potentials - physiology ; Addictive behaviors ; Adrenergic Neurons - drug effects ; Adrenergic Neurons - metabolism ; Anesthesiology ; Animals ; Behavior ; Biological and medical sciences ; Corticotropin-releasing hormone ; Drug abuse ; Drug addictions ; Drug withdrawal ; Laboratory animals ; Localization ; Locus Coeruleus - drug effects ; Locus Coeruleus - metabolism ; Locus Coeruleus - physiopathology ; Male ; Medical sciences ; Mental disorders ; Naloxone - pharmacology ; Narcotic Antagonists - pharmacology ; Narcotics ; Neurobiology ; Neurosciences ; Opioid-Related Disorders - complications ; Opioid-Related Disorders - metabolism ; Opioid-Related Disorders - pathology ; Opioid-Related Disorders - physiopathology ; Opioid-Related Disorders - psychology ; Original ; Rats ; Receptors, Corticotropin-Releasing Hormone - metabolism ; Receptors, Opioid, mu - antagonists & inhibitors ; Receptors, Opioid, mu - metabolism ; Stress ; Stress response ; Stress, Psychological - complications ; Stress, Psychological - metabolism ; Stress, Psychological - physiopathology ; Stress, Psychological - psychology ; Substance Withdrawal Syndrome - psychology ; Toxicology</subject><ispartof>Neuropsychopharmacology (New York, N.Y.), 2013-09, Vol.38 (10), p.1833-1843</ispartof><rights>2014 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Sep 2013</rights><rights>Copyright © 2013 American College of Neuropsychopharmacology 2013 American College of Neuropsychopharmacology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c566t-57a24172de09f283a0896337b18d50fe48f5e8549ae95418d4c437f33922ebb93</citedby><cites>FETCH-LOGICAL-c566t-57a24172de09f283a0896337b18d50fe48f5e8549ae95418d4c437f33922ebb93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3746692/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3746692/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,728,781,785,886,27926,27927,53793,53795</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27682873$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23660707$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>CHAIJALE, Nayla N</creatorcontrib><creatorcontrib>CURTIS, Andre L</creatorcontrib><creatorcontrib>WOOD, Susan K</creatorcontrib><creatorcontrib>ZHANG, Xiao-Yan</creatorcontrib><creatorcontrib>BHATNAGAR, Seema</creatorcontrib><creatorcontrib>REYES, Beverly As</creatorcontrib><creatorcontrib>VAN BOCKSTAELE, Elisabeth J</creatorcontrib><creatorcontrib>VALENTINO, Rita J</creatorcontrib><title>Social Stress Engages Opioid Regulation of Locus Coeruleus Norepinephrine Neurons and Induces a State of Cellular and Physical Opiate Dependence</title><title>Neuropsychopharmacology (New York, N.Y.)</title><addtitle>Neuropsychopharmacology</addtitle><description>Stress is implicated in diverse psychiatric disorders including substance abuse. The locus coeruleus-norepinephrine (LC-NE) system is a major stress response system that is also a point of intersection between stress neuromediators and endogenous opioids and so may be a site at which stress can influence drug-taking behaviors. As social stress is a common stressor for humans, this study characterized the enduring impact of repeated social stress on LC neuronal activity. Rats were exposed to five daily consecutive sessions of social stress using the resident-intruder model or control manipulation. LC discharge rate recorded 2 days after the last manipulation was decreased in stressed rats compared with controls. By 10 days after the last manipulation, LC rates were comparable between groups. Systemic administration of the opiate antagonist, naloxone, robustly increased LC discharge rate in a manner suggestive of opiate withdrawal, selectively in stressed rats when administered 2 or 10 days after the last manipulation. 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This was accompanied by behavioral signs of mild opiate withdrawal. Western blot and electron microscopic studies indicated that repeated social stress decreased corticotropin-releasing factor type 1 receptor and increased μ-opioid receptor levels in the LC. Together, the results suggest that repeated social stress engages endogenous opioid modulation of LC activity and induces signs of cellular and physical opiate dependence that endure after the stress. These cellular effects may predispose individuals with a history of repeated social stress to substance abuse behaviors.</abstract><cop>Basingstoke</cop><pub>Nature Publishing Group</pub><pmid>23660707</pmid><doi>10.1038/npp.2013.117</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| issn | 0893-133X 1740-634X |
| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Action Potentials - drug effects Action Potentials - physiology Addictive behaviors Adrenergic Neurons - drug effects Adrenergic Neurons - metabolism Anesthesiology Animals Behavior Biological and medical sciences Corticotropin-releasing hormone Drug abuse Drug addictions Drug withdrawal Laboratory animals Localization Locus Coeruleus - drug effects Locus Coeruleus - metabolism Locus Coeruleus - physiopathology Male Medical sciences Mental disorders Naloxone - pharmacology Narcotic Antagonists - pharmacology Narcotics Neurobiology Neurosciences Opioid-Related Disorders - complications Opioid-Related Disorders - metabolism Opioid-Related Disorders - pathology Opioid-Related Disorders - physiopathology Opioid-Related Disorders - psychology Original Rats Receptors, Corticotropin-Releasing Hormone - metabolism Receptors, Opioid, mu - antagonists & inhibitors Receptors, Opioid, mu - metabolism Stress Stress response Stress, Psychological - complications Stress, Psychological - metabolism Stress, Psychological - physiopathology Stress, Psychological - psychology Substance Withdrawal Syndrome - psychology Toxicology |
| title | Social Stress Engages Opioid Regulation of Locus Coeruleus Norepinephrine Neurons and Induces a State of Cellular and Physical Opiate Dependence |
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