Long-term fluoxetine produces behavioral anxiolytic effects without inhibiting neuroendocrine responses to conditioned stress in rats
The aim of the present study was to investigate the anxiolytic effects of long-term treatment with fluoxetine in rats. Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, are used to treat anxiety and panic disorders, in addition to treating depression. A major concern with SSRIs is...
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| Veröffentlicht in: | Brain research 2000-02, Vol.855 (1), p.58-66 |
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| creator | Zhang, Yahong Raap, Danı́ K Garcia, Francisca Serres, Florence Ma, Qing Battaglia, George Van de Kar, Louis D |
| description | The aim of the present study was to investigate the anxiolytic effects of long-term treatment with fluoxetine in rats. Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, are used to treat anxiety and panic disorders, in addition to treating depression. A major concern with SSRIs is a 2–3-week delay in their therapeutic effects. SSRIs share with anxiolytic 5-HT
1A agonists the ability to produce desensitization of post-synaptic 5-HT
1A receptors. To investigate the anxiolytic effects of fluoxetine, rats were treated for 14 days with fluoxetine (10 mg kg
−1 day
−1, i.p.). The rats were stressed using a conditioned stress procedure and tested one day after the last fluoxetine injection. Fluoxetine decreased stress-induced defecation (by 60%), reversed the stress-induced suppression of exploring behavior (by 59%) and shortened the duration of stress-induced freezing behavior (by 11.5%). However, the stress-induced increase in plasma levels of ACTH, corticosterone, oxytocin, prolactin and renin were not inhibited by fluoxetine treatment. These findings suggest that neuroadaptive changes induced by sustained inhibition of serotonin (5-HT) reuptake, contribute to the mechanism of the anxiolytic effects of fluoxetine. In contrast, the neuroendocrine responses to conditioned stress are not affected by these neuroadaptive changes. |
| doi_str_mv | 10.1016/S0006-8993(99)02289-1 |
| format | Article |
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1A agonists the ability to produce desensitization of post-synaptic 5-HT
1A receptors. To investigate the anxiolytic effects of fluoxetine, rats were treated for 14 days with fluoxetine (10 mg kg
−1 day
−1, i.p.). The rats were stressed using a conditioned stress procedure and tested one day after the last fluoxetine injection. Fluoxetine decreased stress-induced defecation (by 60%), reversed the stress-induced suppression of exploring behavior (by 59%) and shortened the duration of stress-induced freezing behavior (by 11.5%). However, the stress-induced increase in plasma levels of ACTH, corticosterone, oxytocin, prolactin and renin were not inhibited by fluoxetine treatment. These findings suggest that neuroadaptive changes induced by sustained inhibition of serotonin (5-HT) reuptake, contribute to the mechanism of the anxiolytic effects of fluoxetine. In contrast, the neuroendocrine responses to conditioned stress are not affected by these neuroadaptive changes.</description><identifier>ISSN: 0006-8993</identifier><identifier>EISSN: 1872-6240</identifier><identifier>DOI: 10.1016/S0006-8993(99)02289-1</identifier><identifier>PMID: 10650130</identifier><identifier>CODEN: BRREAP</identifier><language>eng</language><publisher>London: Elsevier B.V</publisher><subject>ACTH ; Adrenocorticotropic Hormone - blood ; Animals ; Anxiety ; Anxiety - drug therapy ; Anxiety - physiopathology ; Behavior, Animal - drug effects ; Biological and medical sciences ; Body Weight ; Conditioning (Psychology) - drug effects ; Corticosterone - blood ; Defecation ; Fluoxetine - pharmacology ; Male ; Medical sciences ; Neuropharmacology ; Neurosecretory Systems - chemistry ; Neurosecretory Systems - drug effects ; Oxytocin ; Oxytocin - blood ; Pharmacology. Drug treatments ; Prolactin ; Prolactin - blood ; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) ; Psychology. Psychoanalysis. Psychiatry ; Psychopharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Serotonin - physiology ; Receptors, Serotonin, 5-HT1 ; Renin ; Renin - blood ; Serotonin ; Serotonin Uptake Inhibitors - pharmacology ; SSRI ; Stress, Physiological - drug therapy ; Stress, Physiological - physiopathology</subject><ispartof>Brain research, 2000-02, Vol.855 (1), p.58-66</ispartof><rights>2000 Elsevier Science B.V.</rights><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c487t-f67a25e4db5255150ca0b6e19aa2b058edb61167136eb23efc6b7819d917aa563</citedby><cites>FETCH-LOGICAL-c487t-f67a25e4db5255150ca0b6e19aa2b058edb61167136eb23efc6b7819d917aa563</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0006-8993(99)02289-1$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1265637$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10650130$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Yahong</creatorcontrib><creatorcontrib>Raap, Danı́ K</creatorcontrib><creatorcontrib>Garcia, Francisca</creatorcontrib><creatorcontrib>Serres, Florence</creatorcontrib><creatorcontrib>Ma, Qing</creatorcontrib><creatorcontrib>Battaglia, George</creatorcontrib><creatorcontrib>Van de Kar, Louis D</creatorcontrib><title>Long-term fluoxetine produces behavioral anxiolytic effects without inhibiting neuroendocrine responses to conditioned stress in rats</title><title>Brain research</title><addtitle>Brain Res</addtitle><description>The aim of the present study was to investigate the anxiolytic effects of long-term treatment with fluoxetine in rats. Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, are used to treat anxiety and panic disorders, in addition to treating depression. A major concern with SSRIs is a 2–3-week delay in their therapeutic effects. SSRIs share with anxiolytic 5-HT
1A agonists the ability to produce desensitization of post-synaptic 5-HT
1A receptors. To investigate the anxiolytic effects of fluoxetine, rats were treated for 14 days with fluoxetine (10 mg kg
−1 day
−1, i.p.). The rats were stressed using a conditioned stress procedure and tested one day after the last fluoxetine injection. Fluoxetine decreased stress-induced defecation (by 60%), reversed the stress-induced suppression of exploring behavior (by 59%) and shortened the duration of stress-induced freezing behavior (by 11.5%). However, the stress-induced increase in plasma levels of ACTH, corticosterone, oxytocin, prolactin and renin were not inhibited by fluoxetine treatment. These findings suggest that neuroadaptive changes induced by sustained inhibition of serotonin (5-HT) reuptake, contribute to the mechanism of the anxiolytic effects of fluoxetine. In contrast, the neuroendocrine responses to conditioned stress are not affected by these neuroadaptive changes.</description><subject>ACTH</subject><subject>Adrenocorticotropic Hormone - blood</subject><subject>Animals</subject><subject>Anxiety</subject><subject>Anxiety - drug therapy</subject><subject>Anxiety - physiopathology</subject><subject>Behavior, Animal - drug effects</subject><subject>Biological and medical sciences</subject><subject>Body Weight</subject><subject>Conditioning (Psychology) - drug effects</subject><subject>Corticosterone - blood</subject><subject>Defecation</subject><subject>Fluoxetine - pharmacology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Neuropharmacology</subject><subject>Neurosecretory Systems - chemistry</subject><subject>Neurosecretory Systems - drug effects</subject><subject>Oxytocin</subject><subject>Oxytocin - blood</subject><subject>Pharmacology. Drug treatments</subject><subject>Prolactin</subject><subject>Prolactin - blood</subject><subject>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Serotonin - physiology</subject><subject>Receptors, Serotonin, 5-HT1</subject><subject>Renin</subject><subject>Renin - blood</subject><subject>Serotonin</subject><subject>Serotonin Uptake Inhibitors - pharmacology</subject><subject>SSRI</subject><subject>Stress, Physiological - drug therapy</subject><subject>Stress, Physiological - physiopathology</subject><issn>0006-8993</issn><issn>1872-6240</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcuOFCEUhonROO3oI2hYGKOLUi4NFCtjJt6STlyoa8Ll1DSmGlqgxpkH8L2lpzvqblaE8P0_HD6EnlLymhIq33wlhMhh1Jq_1PoVYWzUA72HVnRUbJBsTe6j1V_kDD2q9Uffcq7JQ3RGiRSEcrJCvzc5XQ4Nyg5P85KvocUEeF9yWDxU7GBrr2IudsY2Xcc837ToMUwT-Fbxr9i2eWk4pm10sScvcYKlZEgh-3IoKlD3OdXe1DL2OYVO5QQB19aPak_iYlt9jB5Mdq7w5LSeo-8f3n-7-DRsvnz8fPFuM_j1qNowSWWZgHVwgglBBfGWOAlUW8scESMEJymVinIJjnGYvHRqpDpoqqwVkp-jF8fePuDPBWozu1g9zLNNkJdqFBmVoJrfCVK15pJr2kFxBH3JtRaYzL7EnS03hhJzEGVuRZmDBaO1uRVlDrlnpwsWt4PwX-popgPPT4Ct3s5TscnH-o9jss-jOvb2iEH_tqsIxVQfIXkIsXRHJuR4x0v-ABlaszw</recordid><startdate>20000207</startdate><enddate>20000207</enddate><creator>Zhang, Yahong</creator><creator>Raap, Danı́ K</creator><creator>Garcia, Francisca</creator><creator>Serres, Florence</creator><creator>Ma, Qing</creator><creator>Battaglia, George</creator><creator>Van de Kar, Louis D</creator><general>Elsevier B.V</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>7X8</scope></search><sort><creationdate>20000207</creationdate><title>Long-term fluoxetine produces behavioral anxiolytic effects without inhibiting neuroendocrine responses to conditioned stress in rats</title><author>Zhang, Yahong ; Raap, Danı́ K ; Garcia, Francisca ; Serres, Florence ; Ma, Qing ; Battaglia, George ; Van de Kar, Louis D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c487t-f67a25e4db5255150ca0b6e19aa2b058edb61167136eb23efc6b7819d917aa563</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>ACTH</topic><topic>Adrenocorticotropic Hormone - blood</topic><topic>Animals</topic><topic>Anxiety</topic><topic>Anxiety - drug therapy</topic><topic>Anxiety - physiopathology</topic><topic>Behavior, Animal - drug effects</topic><topic>Biological and medical sciences</topic><topic>Body Weight</topic><topic>Conditioning (Psychology) - drug effects</topic><topic>Corticosterone - blood</topic><topic>Defecation</topic><topic>Fluoxetine - pharmacology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Neuropharmacology</topic><topic>Neurosecretory Systems - chemistry</topic><topic>Neurosecretory Systems - drug effects</topic><topic>Oxytocin</topic><topic>Oxytocin - blood</topic><topic>Pharmacology. Drug treatments</topic><topic>Prolactin</topic><topic>Prolactin - blood</topic><topic>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, Serotonin - physiology</topic><topic>Receptors, Serotonin, 5-HT1</topic><topic>Renin</topic><topic>Renin - blood</topic><topic>Serotonin</topic><topic>Serotonin Uptake Inhibitors - pharmacology</topic><topic>SSRI</topic><topic>Stress, Physiological - drug therapy</topic><topic>Stress, Physiological - physiopathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Yahong</creatorcontrib><creatorcontrib>Raap, Danı́ K</creatorcontrib><creatorcontrib>Garcia, Francisca</creatorcontrib><creatorcontrib>Serres, Florence</creatorcontrib><creatorcontrib>Ma, Qing</creatorcontrib><creatorcontrib>Battaglia, George</creatorcontrib><creatorcontrib>Van de Kar, Louis D</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>MEDLINE - Academic</collection><jtitle>Brain research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Yahong</au><au>Raap, Danı́ K</au><au>Garcia, Francisca</au><au>Serres, Florence</au><au>Ma, Qing</au><au>Battaglia, George</au><au>Van de Kar, Louis D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Long-term fluoxetine produces behavioral anxiolytic effects without inhibiting neuroendocrine responses to conditioned stress in rats</atitle><jtitle>Brain research</jtitle><addtitle>Brain Res</addtitle><date>2000-02-07</date><risdate>2000</risdate><volume>855</volume><issue>1</issue><spage>58</spage><epage>66</epage><pages>58-66</pages><issn>0006-8993</issn><eissn>1872-6240</eissn><coden>BRREAP</coden><abstract>The aim of the present study was to investigate the anxiolytic effects of long-term treatment with fluoxetine in rats. Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, are used to treat anxiety and panic disorders, in addition to treating depression. A major concern with SSRIs is a 2–3-week delay in their therapeutic effects. SSRIs share with anxiolytic 5-HT
1A agonists the ability to produce desensitization of post-synaptic 5-HT
1A receptors. To investigate the anxiolytic effects of fluoxetine, rats were treated for 14 days with fluoxetine (10 mg kg
−1 day
−1, i.p.). The rats were stressed using a conditioned stress procedure and tested one day after the last fluoxetine injection. Fluoxetine decreased stress-induced defecation (by 60%), reversed the stress-induced suppression of exploring behavior (by 59%) and shortened the duration of stress-induced freezing behavior (by 11.5%). However, the stress-induced increase in plasma levels of ACTH, corticosterone, oxytocin, prolactin and renin were not inhibited by fluoxetine treatment. These findings suggest that neuroadaptive changes induced by sustained inhibition of serotonin (5-HT) reuptake, contribute to the mechanism of the anxiolytic effects of fluoxetine. In contrast, the neuroendocrine responses to conditioned stress are not affected by these neuroadaptive changes.</abstract><cop>London</cop><cop>Amsterdam</cop><cop>New York, NY</cop><pub>Elsevier B.V</pub><pmid>10650130</pmid><doi>10.1016/S0006-8993(99)02289-1</doi><tpages>9</tpages></addata></record> |
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| subjects | ACTH Adrenocorticotropic Hormone - blood Animals Anxiety Anxiety - drug therapy Anxiety - physiopathology Behavior, Animal - drug effects Biological and medical sciences Body Weight Conditioning (Psychology) - drug effects Corticosterone - blood Defecation Fluoxetine - pharmacology Male Medical sciences Neuropharmacology Neurosecretory Systems - chemistry Neurosecretory Systems - drug effects Oxytocin Oxytocin - blood Pharmacology. Drug treatments Prolactin Prolactin - blood Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) Psychology. Psychoanalysis. Psychiatry Psychopharmacology Rats Rats, Sprague-Dawley Receptors, Serotonin - physiology Receptors, Serotonin, 5-HT1 Renin Renin - blood Serotonin Serotonin Uptake Inhibitors - pharmacology SSRI Stress, Physiological - drug therapy Stress, Physiological - physiopathology |
| title | Long-term fluoxetine produces behavioral anxiolytic effects without inhibiting neuroendocrine responses to conditioned stress in rats |
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