Prolonged fear incubation leads to generalized avoidance behavior in mice
Abstract Long-lasting presence of avoidance and emotional numbing are reliable behavioral markers for PTSD, but little is known about its psychological and biological underpinnings. We employed our recently established mouse model of PTSD (i) to study the emergence of avoidance behavior in the after...
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| Veröffentlicht in: | Journal of psychiatric research 2011-03, Vol.45 (3), p.354-360 |
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| creator | Pamplona, F.A Henes, K Micale, V Mauch, C.P Takahashi, R.N Wotjak, C.T |
| description | Abstract Long-lasting presence of avoidance and emotional numbing are reliable behavioral markers for PTSD, but little is known about its psychological and biological underpinnings. We employed our recently established mouse model of PTSD (i) to study the emergence of avoidance behavior in the aftermath of a trauma, (ii) to disentangle the impact of context generalization vs. lack of motivation vs. novelty fear and (iii) to assess the therapeutic value of benzodiazepines and selective serotonin reuptake inhibitors (SSRIs). Specific conditioned avoidance to shock-paired odor turned into generalized avoidance after 28 days of fear incubation. Combination of habituation to the novel environment and extinction of contextual fear abolished both generalized and specific avoidance behavior. Chronic fluoxetine treatment partially reversed the phenotype, whereas acute treatment with diazepam did not. Our animal model may help understanding the mechanisms underlying psychological and biological mechanisms of PTSD for the benefit of developing pharmacotherapeutic strategies, which specifically address generalized avoidance. |
| doi_str_mv | 10.1016/j.jpsychires.2010.06.015 |
| format | Article |
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We employed our recently established mouse model of PTSD (i) to study the emergence of avoidance behavior in the aftermath of a trauma, (ii) to disentangle the impact of context generalization vs. lack of motivation vs. novelty fear and (iii) to assess the therapeutic value of benzodiazepines and selective serotonin reuptake inhibitors (SSRIs). Specific conditioned avoidance to shock-paired odor turned into generalized avoidance after 28 days of fear incubation. Combination of habituation to the novel environment and extinction of contextual fear abolished both generalized and specific avoidance behavior. Chronic fluoxetine treatment partially reversed the phenotype, whereas acute treatment with diazepam did not. Our animal model may help understanding the mechanisms underlying psychological and biological mechanisms of PTSD for the benefit of developing pharmacotherapeutic strategies, which specifically address generalized avoidance.</description><identifier>ISSN: 0022-3956</identifier><identifier>EISSN: 1879-1379</identifier><identifier>DOI: 10.1016/j.jpsychires.2010.06.015</identifier><identifier>PMID: 20655545</identifier><identifier>CODEN: JPYRA3</identifier><language>eng</language><publisher>Kidlington: Elsevier Ltd</publisher><subject>Adult and adolescent clinical studies ; Animals ; Antidepressive Agents, Second-Generation ; Anxiety disorders. Neuroses ; Avoidance ; Avoidance behaviour ; Avoidance Learning - drug effects ; Behavior, Animal ; Biological and medical sciences ; Conditioned fear ; Conditioning, Classical - drug effects ; Diazepam - pharmacology ; Electroshock - adverse effects ; Extinction, Psychological - drug effects ; Fear ; Fear - drug effects ; Fear incubation ; Fluoxetine - pharmacology ; Habituation, Psychophysiologic ; Hypnotics and Sedatives - pharmacology ; Indexing in process ; Male ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Odorants ; Post-traumatic stress disorder ; Posttraumatic stress disorder ; Psychiatry ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; PTSD ; Serotonin reuptake inhibitors ; Time Factors</subject><ispartof>Journal of psychiatric research, 2011-03, Vol.45 (3), p.354-360</ispartof><rights>Elsevier Ltd</rights><rights>2010 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2010 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c676t-f2459a8e616add54c4a1d3816a75c06cdfda42915572ec09d8d7038ca4949b8e3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jpsychires.2010.06.015$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,31005,46000</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23933100$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20655545$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pamplona, F.A</creatorcontrib><creatorcontrib>Henes, K</creatorcontrib><creatorcontrib>Micale, V</creatorcontrib><creatorcontrib>Mauch, C.P</creatorcontrib><creatorcontrib>Takahashi, R.N</creatorcontrib><creatorcontrib>Wotjak, C.T</creatorcontrib><title>Prolonged fear incubation leads to generalized avoidance behavior in mice</title><title>Journal of psychiatric research</title><addtitle>J Psychiatr Res</addtitle><description>Abstract Long-lasting presence of avoidance and emotional numbing are reliable behavioral markers for PTSD, but little is known about its psychological and biological underpinnings. We employed our recently established mouse model of PTSD (i) to study the emergence of avoidance behavior in the aftermath of a trauma, (ii) to disentangle the impact of context generalization vs. lack of motivation vs. novelty fear and (iii) to assess the therapeutic value of benzodiazepines and selective serotonin reuptake inhibitors (SSRIs). Specific conditioned avoidance to shock-paired odor turned into generalized avoidance after 28 days of fear incubation. Combination of habituation to the novel environment and extinction of contextual fear abolished both generalized and specific avoidance behavior. Chronic fluoxetine treatment partially reversed the phenotype, whereas acute treatment with diazepam did not. Our animal model may help understanding the mechanisms underlying psychological and biological mechanisms of PTSD for the benefit of developing pharmacotherapeutic strategies, which specifically address generalized avoidance.</description><subject>Adult and adolescent clinical studies</subject><subject>Animals</subject><subject>Antidepressive Agents, Second-Generation</subject><subject>Anxiety disorders. Neuroses</subject><subject>Avoidance</subject><subject>Avoidance behaviour</subject><subject>Avoidance Learning - drug effects</subject><subject>Behavior, Animal</subject><subject>Biological and medical sciences</subject><subject>Conditioned fear</subject><subject>Conditioning, Classical - drug effects</subject><subject>Diazepam - pharmacology</subject><subject>Electroshock - adverse effects</subject><subject>Extinction, Psychological - drug effects</subject><subject>Fear</subject><subject>Fear - drug effects</subject><subject>Fear incubation</subject><subject>Fluoxetine - pharmacology</subject><subject>Habituation, Psychophysiologic</subject><subject>Hypnotics and Sedatives - pharmacology</subject><subject>Indexing in process</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Odorants</subject><subject>Post-traumatic stress disorder</subject><subject>Posttraumatic stress disorder</subject><subject>Psychiatry</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>PTSD</subject><subject>Serotonin reuptake inhibitors</subject><subject>Time Factors</subject><issn>0022-3956</issn><issn>1879-1379</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>7QJ</sourceid><recordid>eNqNkk2LFDEQQIMo7uzqX5C-iF56rCSddHIRdHF1YUFBPYdMUr2btqczJt0D4683zYwueFBPocKrD-oVIRWFNQUqX_XrfpcP7i4kzGsG5RvkGqh4QFZUtbqmvNUPyQqAsZprIc_Iec49ALSMNo_JGQMphGjEilx_SnGI4y36qkObqjC6eWOnEMdqQOtzNcXqFkdMdgg_CmT3MXg7Oqw2eGf3IS4p1TY4fEIedXbI-PT0XpCvV---XH6obz6-v758c1M72cqp7lgjtFUoqbTei8Y1lnquStQKB9L5ztuGaSpEy9CB9sq3wJWzjW70RiG_IC-OdXcpfp8xT2YbssNhsCPGORvVgtaC0ubfpOCMCcpkIV_-laSUCca1Zqqg6oi6FHNO2JldClubDoaCWeSY3tzLMYscA9IUOSX12anLvNmi_534y0YBnp8Am50dulQWHfI9xzXnFKBwb48clj3vAyaTXcAixZeebjI-hv-Z5vUfRdwQxlD6fsMD5j7OaSweDTWZGTCfl2NabqkMAKUO5z8BUlHGXA</recordid><startdate>20110301</startdate><enddate>20110301</enddate><creator>Pamplona, F.A</creator><creator>Henes, K</creator><creator>Micale, V</creator><creator>Mauch, C.P</creator><creator>Takahashi, R.N</creator><creator>Wotjak, C.T</creator><general>Elsevier Ltd</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>7TK</scope><scope>7X8</scope><scope>7QJ</scope></search><sort><creationdate>20110301</creationdate><title>Prolonged fear incubation leads to generalized avoidance behavior in mice</title><author>Pamplona, F.A ; Henes, K ; Micale, V ; Mauch, C.P ; Takahashi, R.N ; Wotjak, C.T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c676t-f2459a8e616add54c4a1d3816a75c06cdfda42915572ec09d8d7038ca4949b8e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adult and adolescent clinical studies</topic><topic>Animals</topic><topic>Antidepressive Agents, Second-Generation</topic><topic>Anxiety disorders. Neuroses</topic><topic>Avoidance</topic><topic>Avoidance behaviour</topic><topic>Avoidance Learning - drug effects</topic><topic>Behavior, Animal</topic><topic>Biological and medical sciences</topic><topic>Conditioned fear</topic><topic>Conditioning, Classical - drug effects</topic><topic>Diazepam - pharmacology</topic><topic>Electroshock - adverse effects</topic><topic>Extinction, Psychological - drug effects</topic><topic>Fear</topic><topic>Fear - drug effects</topic><topic>Fear incubation</topic><topic>Fluoxetine - pharmacology</topic><topic>Habituation, Psychophysiologic</topic><topic>Hypnotics and Sedatives - pharmacology</topic><topic>Indexing in process</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Odorants</topic><topic>Post-traumatic stress disorder</topic><topic>Posttraumatic stress disorder</topic><topic>Psychiatry</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><topic>PTSD</topic><topic>Serotonin reuptake inhibitors</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pamplona, F.A</creatorcontrib><creatorcontrib>Henes, K</creatorcontrib><creatorcontrib>Micale, V</creatorcontrib><creatorcontrib>Mauch, C.P</creatorcontrib><creatorcontrib>Takahashi, R.N</creatorcontrib><creatorcontrib>Wotjak, C.T</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>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Applied Social Sciences Index & Abstracts (ASSIA)</collection><jtitle>Journal of psychiatric research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pamplona, F.A</au><au>Henes, K</au><au>Micale, V</au><au>Mauch, C.P</au><au>Takahashi, R.N</au><au>Wotjak, C.T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prolonged fear incubation leads to generalized avoidance behavior in mice</atitle><jtitle>Journal of psychiatric research</jtitle><addtitle>J Psychiatr Res</addtitle><date>2011-03-01</date><risdate>2011</risdate><volume>45</volume><issue>3</issue><spage>354</spage><epage>360</epage><pages>354-360</pages><issn>0022-3956</issn><eissn>1879-1379</eissn><coden>JPYRA3</coden><abstract>Abstract Long-lasting presence of avoidance and emotional numbing are reliable behavioral markers for PTSD, but little is known about its psychological and biological underpinnings. We employed our recently established mouse model of PTSD (i) to study the emergence of avoidance behavior in the aftermath of a trauma, (ii) to disentangle the impact of context generalization vs. lack of motivation vs. novelty fear and (iii) to assess the therapeutic value of benzodiazepines and selective serotonin reuptake inhibitors (SSRIs). Specific conditioned avoidance to shock-paired odor turned into generalized avoidance after 28 days of fear incubation. Combination of habituation to the novel environment and extinction of contextual fear abolished both generalized and specific avoidance behavior. Chronic fluoxetine treatment partially reversed the phenotype, whereas acute treatment with diazepam did not. 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| subjects | Adult and adolescent clinical studies Animals Antidepressive Agents, Second-Generation Anxiety disorders. Neuroses Avoidance Avoidance behaviour Avoidance Learning - drug effects Behavior, Animal Biological and medical sciences Conditioned fear Conditioning, Classical - drug effects Diazepam - pharmacology Electroshock - adverse effects Extinction, Psychological - drug effects Fear Fear - drug effects Fear incubation Fluoxetine - pharmacology Habituation, Psychophysiologic Hypnotics and Sedatives - pharmacology Indexing in process Male Medical sciences Mice Mice, Inbred C57BL Odorants Post-traumatic stress disorder Posttraumatic stress disorder Psychiatry Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry PTSD Serotonin reuptake inhibitors Time Factors |
| title | Prolonged fear incubation leads to generalized avoidance behavior in mice |
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