Hcrtr1 and 2 signaling differentially regulates depression-like behaviors
► Orexin receptors 1 and 2 differentially modulate depression like behavior. ► Disruption of orexin receptor 1 decreases behavioral despair while disruption of orexin receptor 2 enhances this behavior. ► No effect of orexin receptor deletion was observed in measures of anxiety like behavior or in op...
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| Veröffentlicht in: | Behavioural brain research 2011-09, Vol.222 (2), p.289-294 |
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| creator | Scott, Michael M. Marcus, Jacob N. Pettersen, Ami Birnbaum, Shari G. Mochizuki, Takatoshi Scammell, Thomas E. Nestler, Eric J. Elmquist, Joel K. Lutter, Michael |
| description | ► Orexin receptors 1 and 2 differentially modulate depression like behavior. ► Disruption of orexin receptor 1 decreases behavioral despair while disruption of orexin receptor 2 enhances this behavior. ► No effect of orexin receptor deletion was observed in measures of anxiety like behavior or in open field locomotion. ► The novel orexin receptor null mouse lines described in this report will be useful in future studies of orexinergic modulation of behavior.
The orexin/hypocretin system has the potential to significantly modulate affect, based on both the neuroanatomical projection patterns of these neurons and on the sites of orexin receptor expression. However, there is little data supporting the role of specific orexin receptors in the modulation of depression-like behavior. Here we report behavioral profiling of mice after genetic or pharmacologic inhibition of hcrtr1 and 2 receptor signaling. Hcrtr1 null mice displayed a significant reduction in behavioral despair in the forced swim test and tail suspension test. Wild-type mice treated with the hcrtr1 antagonist SB-334867 also displayed a similar reduction in behavioral despair. No difference in anxiety-like behavior was noted following hcrtr1 deletion. In contrast, hcrtr2-null mice displayed an increase in behavioral despair with no effect on measures of anxiety. These studies suggest that the balance of orexin action at either the hcrtr1 or the hcrtr2 receptor produces an anti-depressant or pro-depressant like effect, depending on the receptor subtype activated. |
| doi_str_mv | 10.1016/j.bbr.2011.02.044 |
| format | Article |
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The orexin/hypocretin system has the potential to significantly modulate affect, based on both the neuroanatomical projection patterns of these neurons and on the sites of orexin receptor expression. However, there is little data supporting the role of specific orexin receptors in the modulation of depression-like behavior. Here we report behavioral profiling of mice after genetic or pharmacologic inhibition of hcrtr1 and 2 receptor signaling. Hcrtr1 null mice displayed a significant reduction in behavioral despair in the forced swim test and tail suspension test. Wild-type mice treated with the hcrtr1 antagonist SB-334867 also displayed a similar reduction in behavioral despair. No difference in anxiety-like behavior was noted following hcrtr1 deletion. In contrast, hcrtr2-null mice displayed an increase in behavioral despair with no effect on measures of anxiety. These studies suggest that the balance of orexin action at either the hcrtr1 or the hcrtr2 receptor produces an anti-depressant or pro-depressant like effect, depending on the receptor subtype activated.</description><identifier>ISSN: 0166-4328</identifier><identifier>EISSN: 1872-7549</identifier><identifier>DOI: 10.1016/j.bbr.2011.02.044</identifier><identifier>PMID: 21377495</identifier><identifier>CODEN: BBREDI</identifier><language>eng</language><publisher>Shannon: Elsevier B.V</publisher><subject>Adult and adolescent clinical studies ; Animals ; Anxiety ; Anxiety - genetics ; Behavioral psychophysiology ; Benzoxazoles - pharmacology ; Benzoxazoles - therapeutic use ; Biological and medical sciences ; Choice Behavior - drug effects ; Choice Behavior - physiology ; Depression ; Depression - drug therapy ; Depression - genetics ; Depression - physiopathology ; Disease Models, Animal ; Fundamental and applied biological sciences. Psychology ; Immobility Response, Tonic - drug effects ; Immobility Response, Tonic - physiology ; Male ; Maze Learning - drug effects ; Maze Learning - physiology ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mood disorders ; Motor Activity - drug effects ; Motor Activity - physiology ; Orexin ; Orexin Receptors ; Psychology. Psychoanalysis. Psychiatry ; Psychology. Psychophysiology ; Psychopathology. Psychiatry ; Receptors, G-Protein-Coupled - antagonists & inhibitors ; Receptors, G-Protein-Coupled - genetics ; Receptors, G-Protein-Coupled - physiology ; Receptors, Neuropeptide - antagonists & inhibitors ; Receptors, Neuropeptide - genetics ; Receptors, Neuropeptide - physiology ; Signal Transduction - genetics ; Signal Transduction - physiology ; Swimming - physiology ; Urea - analogs & derivatives ; Urea - pharmacology ; Urea - therapeutic use</subject><ispartof>Behavioural brain research, 2011-09, Vol.222 (2), p.289-294</ispartof><rights>2011 Elsevier B.V.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 Elsevier B.V. All rights reserved.</rights><rights>2011 Elsevier B.V. All rights reserved. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c578t-247b9919046df44145ec971ca2580230594e13aa83a125ba875f19a825d9dc1f3</citedby><cites>FETCH-LOGICAL-c578t-247b9919046df44145ec971ca2580230594e13aa83a125ba875f19a825d9dc1f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbr.2011.02.044$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,777,781,882,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24202991$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21377495$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Scott, Michael M.</creatorcontrib><creatorcontrib>Marcus, Jacob N.</creatorcontrib><creatorcontrib>Pettersen, Ami</creatorcontrib><creatorcontrib>Birnbaum, Shari G.</creatorcontrib><creatorcontrib>Mochizuki, Takatoshi</creatorcontrib><creatorcontrib>Scammell, Thomas E.</creatorcontrib><creatorcontrib>Nestler, Eric J.</creatorcontrib><creatorcontrib>Elmquist, Joel K.</creatorcontrib><creatorcontrib>Lutter, Michael</creatorcontrib><title>Hcrtr1 and 2 signaling differentially regulates depression-like behaviors</title><title>Behavioural brain research</title><addtitle>Behav Brain Res</addtitle><description>► Orexin receptors 1 and 2 differentially modulate depression like behavior. ► Disruption of orexin receptor 1 decreases behavioral despair while disruption of orexin receptor 2 enhances this behavior. ► No effect of orexin receptor deletion was observed in measures of anxiety like behavior or in open field locomotion. ► The novel orexin receptor null mouse lines described in this report will be useful in future studies of orexinergic modulation of behavior.
The orexin/hypocretin system has the potential to significantly modulate affect, based on both the neuroanatomical projection patterns of these neurons and on the sites of orexin receptor expression. However, there is little data supporting the role of specific orexin receptors in the modulation of depression-like behavior. Here we report behavioral profiling of mice after genetic or pharmacologic inhibition of hcrtr1 and 2 receptor signaling. Hcrtr1 null mice displayed a significant reduction in behavioral despair in the forced swim test and tail suspension test. Wild-type mice treated with the hcrtr1 antagonist SB-334867 also displayed a similar reduction in behavioral despair. No difference in anxiety-like behavior was noted following hcrtr1 deletion. In contrast, hcrtr2-null mice displayed an increase in behavioral despair with no effect on measures of anxiety. These studies suggest that the balance of orexin action at either the hcrtr1 or the hcrtr2 receptor produces an anti-depressant or pro-depressant like effect, depending on the receptor subtype activated.</description><subject>Adult and adolescent clinical studies</subject><subject>Animals</subject><subject>Anxiety</subject><subject>Anxiety - genetics</subject><subject>Behavioral psychophysiology</subject><subject>Benzoxazoles - pharmacology</subject><subject>Benzoxazoles - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Choice Behavior - drug effects</subject><subject>Choice Behavior - physiology</subject><subject>Depression</subject><subject>Depression - drug therapy</subject><subject>Depression - genetics</subject><subject>Depression - physiopathology</subject><subject>Disease Models, Animal</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Immobility Response, Tonic - drug effects</subject><subject>Immobility Response, Tonic - physiology</subject><subject>Male</subject><subject>Maze Learning - drug effects</subject><subject>Maze Learning - physiology</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Mood disorders</subject><subject>Motor Activity - drug effects</subject><subject>Motor Activity - physiology</subject><subject>Orexin</subject><subject>Orexin Receptors</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychology. Psychophysiology</subject><subject>Psychopathology. Psychiatry</subject><subject>Receptors, G-Protein-Coupled - antagonists & inhibitors</subject><subject>Receptors, G-Protein-Coupled - genetics</subject><subject>Receptors, G-Protein-Coupled - physiology</subject><subject>Receptors, Neuropeptide - antagonists & inhibitors</subject><subject>Receptors, Neuropeptide - genetics</subject><subject>Receptors, Neuropeptide - physiology</subject><subject>Signal Transduction - genetics</subject><subject>Signal Transduction - physiology</subject><subject>Swimming - physiology</subject><subject>Urea - analogs & derivatives</subject><subject>Urea - pharmacology</subject><subject>Urea - therapeutic use</subject><issn>0166-4328</issn><issn>1872-7549</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkcGKFDEQhoMo7jj6AF6kL-Kp21Q66SQIgizqLix40XOoTlfPZsx0j0nPwL69WWZc9SKecqivfv7Ux9hL4A1w6N5um75PjeAADRcNl_IRW4HRotZK2sdsVZiulq0wF-xZzlvOueQKnrILAa3W0qoVu77yaUlQ4TRUosphM2EM06YawjhSomkJGONdlWhziLhQrgbaJ8o5zFMdw3eqerrFY5hTfs6ejBgzvTi_a_bt08evl1f1zZfP15cfbmqvtFlqIXVvLVguu2GUEqQibzV4FMpw0XJlJUGLaFoEoXo0Wo1g0Qg12MHD2K7Z-1Pu_tDvaPClY8Lo9insMN25GYP7ezKFW7eZj66VWgrblYA354A0_zhQXtwuZE8x4kTzITtjWi6Ubf-D7LQ00JXaawYn0qc550TjQx_g7t6V27riyt27cly44qrsvPrzIw8bv-QU4PUZwOwxjgknH_JvTgouyikL9-7EUTn7MVBy2QeaPA0hkV_cMId_1PgJ8XyxZQ</recordid><startdate>20110923</startdate><enddate>20110923</enddate><creator>Scott, Michael M.</creator><creator>Marcus, Jacob N.</creator><creator>Pettersen, Ami</creator><creator>Birnbaum, Shari G.</creator><creator>Mochizuki, Takatoshi</creator><creator>Scammell, Thomas E.</creator><creator>Nestler, Eric J.</creator><creator>Elmquist, Joel K.</creator><creator>Lutter, Michael</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>7X8</scope><scope>7QG</scope><scope>7TK</scope><scope>5PM</scope></search><sort><creationdate>20110923</creationdate><title>Hcrtr1 and 2 signaling differentially regulates depression-like behaviors</title><author>Scott, Michael M. ; Marcus, Jacob N. ; Pettersen, Ami ; Birnbaum, Shari G. ; Mochizuki, Takatoshi ; Scammell, Thomas E. ; Nestler, Eric J. ; Elmquist, Joel K. ; Lutter, Michael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c578t-247b9919046df44145ec971ca2580230594e13aa83a125ba875f19a825d9dc1f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adult and adolescent clinical studies</topic><topic>Animals</topic><topic>Anxiety</topic><topic>Anxiety - genetics</topic><topic>Behavioral psychophysiology</topic><topic>Benzoxazoles - pharmacology</topic><topic>Benzoxazoles - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Choice Behavior - drug effects</topic><topic>Choice Behavior - physiology</topic><topic>Depression</topic><topic>Depression - drug therapy</topic><topic>Depression - genetics</topic><topic>Depression - physiopathology</topic><topic>Disease Models, Animal</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Immobility Response, Tonic - drug effects</topic><topic>Immobility Response, Tonic - physiology</topic><topic>Male</topic><topic>Maze Learning - drug effects</topic><topic>Maze Learning - physiology</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Mood disorders</topic><topic>Motor Activity - drug effects</topic><topic>Motor Activity - physiology</topic><topic>Orexin</topic><topic>Orexin Receptors</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychology. Psychophysiology</topic><topic>Psychopathology. 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The orexin/hypocretin system has the potential to significantly modulate affect, based on both the neuroanatomical projection patterns of these neurons and on the sites of orexin receptor expression. However, there is little data supporting the role of specific orexin receptors in the modulation of depression-like behavior. Here we report behavioral profiling of mice after genetic or pharmacologic inhibition of hcrtr1 and 2 receptor signaling. Hcrtr1 null mice displayed a significant reduction in behavioral despair in the forced swim test and tail suspension test. Wild-type mice treated with the hcrtr1 antagonist SB-334867 also displayed a similar reduction in behavioral despair. No difference in anxiety-like behavior was noted following hcrtr1 deletion. In contrast, hcrtr2-null mice displayed an increase in behavioral despair with no effect on measures of anxiety. These studies suggest that the balance of orexin action at either the hcrtr1 or the hcrtr2 receptor produces an anti-depressant or pro-depressant like effect, depending on the receptor subtype activated.</abstract><cop>Shannon</cop><pub>Elsevier B.V</pub><pmid>21377495</pmid><doi>10.1016/j.bbr.2011.02.044</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult and adolescent clinical studies Animals Anxiety Anxiety - genetics Behavioral psychophysiology Benzoxazoles - pharmacology Benzoxazoles - therapeutic use Biological and medical sciences Choice Behavior - drug effects Choice Behavior - physiology Depression Depression - drug therapy Depression - genetics Depression - physiopathology Disease Models, Animal Fundamental and applied biological sciences. Psychology Immobility Response, Tonic - drug effects Immobility Response, Tonic - physiology Male Maze Learning - drug effects Maze Learning - physiology Medical sciences Mice Mice, Inbred C57BL Mice, Knockout Mood disorders Motor Activity - drug effects Motor Activity - physiology Orexin Orexin Receptors Psychology. Psychoanalysis. Psychiatry Psychology. Psychophysiology Psychopathology. Psychiatry Receptors, G-Protein-Coupled - antagonists & inhibitors Receptors, G-Protein-Coupled - genetics Receptors, G-Protein-Coupled - physiology Receptors, Neuropeptide - antagonists & inhibitors Receptors, Neuropeptide - genetics Receptors, Neuropeptide - physiology Signal Transduction - genetics Signal Transduction - physiology Swimming - physiology Urea - analogs & derivatives Urea - pharmacology Urea - therapeutic use |
| title | Hcrtr1 and 2 signaling differentially regulates depression-like behaviors |
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