Cortical and striatal serotonin transporter binding in a genetic rat model of depression and in response to electroconvulsive stimuli
•FSL-depressive rats and control rats were sham-handled or treated with ECS.•SERT density studied in cortex and striatum by quantitative in vitro autoradiography.•FSL rats had higher SERT density than SD control rats under sham conditions.•SD control rats, but not FSL rats, displayed a significant e...
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| Veröffentlicht in: | European neuropsychopharmacology 2019-04, Vol.29 (4), p.493-500 |
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| creator | Hvilsom, Anna Sophie Thue Lillethorup, Thea P. Iversen, Peter Doudet, Doris J. Wegener, Gregers Landau, Anne M. |
| description | •FSL-depressive rats and control rats were sham-handled or treated with ECS.•SERT density studied in cortex and striatum by quantitative in vitro autoradiography.•FSL rats had higher SERT density than SD control rats under sham conditions.•SD control rats, but not FSL rats, displayed a significant effect of ECS treatment.•Data support altered SERT in depression and differential strain-related ECS responses.
Depression is a debilitating mental illness and two thirds of patients respond insufficiently to conventional antidepressants. Electroconvulsive therapy (ECT) remains the most effective treatment to alleviate drug-refractory depression, however the neurobiological mechanisms are mostly unknown. The serotonergic system plays an important role in depression and alterations in the serotonin transporter (SERT) are seen both in depression and response to antidepressant pharmacotherapies. The first aim of this study was to investigate SERT density in a genetic rat model of depression, Flinders Sensitive Line (FSL), compared to control Flinders Resistant Line (FRL) and Sprague-Dawley (SD) rats. The second aim was to investigate SERT density in response to electroconvulsive stimuli (ECS), an animal model of ECT. Female rats of each strain were treated with ECS or sham (ear-clip placement with no current) for 10 days before brains were removed, frozen and cut into 20 µm thick sections. SERT density was measured in striatal and cortical regions by quantitative in vitro autoradiography using the SERT-radioligand, [3H]-DASB. Higher SERT density was observed in FSL rats compared to SD rats by 36–48% in motor cortex and striatum under sham conditions. In response to ECS, SD rats displayed a significant effect of treatment, whereas no changes were observed in FRL and FSL rats. Increased SERT binding in FSL rats compared to SD supports a dysfunction of the serotonergic system in depression. The increased SERT density after ECS, seen in SD rats but not FSL rats, suggests a different mechanism of action between depressive-like rats and controls. |
| doi_str_mv | 10.1016/j.euroneuro.2019.02.009 |
| format | Article |
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Depression is a debilitating mental illness and two thirds of patients respond insufficiently to conventional antidepressants. Electroconvulsive therapy (ECT) remains the most effective treatment to alleviate drug-refractory depression, however the neurobiological mechanisms are mostly unknown. The serotonergic system plays an important role in depression and alterations in the serotonin transporter (SERT) are seen both in depression and response to antidepressant pharmacotherapies. The first aim of this study was to investigate SERT density in a genetic rat model of depression, Flinders Sensitive Line (FSL), compared to control Flinders Resistant Line (FRL) and Sprague-Dawley (SD) rats. The second aim was to investigate SERT density in response to electroconvulsive stimuli (ECS), an animal model of ECT. Female rats of each strain were treated with ECS or sham (ear-clip placement with no current) for 10 days before brains were removed, frozen and cut into 20 µm thick sections. SERT density was measured in striatal and cortical regions by quantitative in vitro autoradiography using the SERT-radioligand, [3H]-DASB. Higher SERT density was observed in FSL rats compared to SD rats by 36–48% in motor cortex and striatum under sham conditions. In response to ECS, SD rats displayed a significant effect of treatment, whereas no changes were observed in FRL and FSL rats. Increased SERT binding in FSL rats compared to SD supports a dysfunction of the serotonergic system in depression. The increased SERT density after ECS, seen in SD rats but not FSL rats, suggests a different mechanism of action between depressive-like rats and controls.</description><identifier>ISSN: 0924-977X</identifier><identifier>EISSN: 1873-7862</identifier><identifier>DOI: 10.1016/j.euroneuro.2019.02.009</identifier><identifier>PMID: 30826156</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Autoradiography ; DASB ; Electroconvulsive therapy ; Flinders resistant line rats ; Flinders sensitive line rats ; Serotonin transporter</subject><ispartof>European neuropsychopharmacology, 2019-04, Vol.29 (4), p.493-500</ispartof><rights>2019</rights><rights>Copyright © 2019. Published by Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c371t-7542981971552711df62ab55cd9223ed597d8474d141d92cef4da974a85e0d773</citedby><cites>FETCH-LOGICAL-c371t-7542981971552711df62ab55cd9223ed597d8474d141d92cef4da974a85e0d773</cites><orcidid>0000-0002-7371-8713</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.euroneuro.2019.02.009$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30826156$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hvilsom, Anna Sophie Thue</creatorcontrib><creatorcontrib>Lillethorup, Thea P.</creatorcontrib><creatorcontrib>Iversen, Peter</creatorcontrib><creatorcontrib>Doudet, Doris J.</creatorcontrib><creatorcontrib>Wegener, Gregers</creatorcontrib><creatorcontrib>Landau, Anne M.</creatorcontrib><title>Cortical and striatal serotonin transporter binding in a genetic rat model of depression and in response to electroconvulsive stimuli</title><title>European neuropsychopharmacology</title><addtitle>Eur Neuropsychopharmacol</addtitle><description>•FSL-depressive rats and control rats were sham-handled or treated with ECS.•SERT density studied in cortex and striatum by quantitative in vitro autoradiography.•FSL rats had higher SERT density than SD control rats under sham conditions.•SD control rats, but not FSL rats, displayed a significant effect of ECS treatment.•Data support altered SERT in depression and differential strain-related ECS responses.
Depression is a debilitating mental illness and two thirds of patients respond insufficiently to conventional antidepressants. Electroconvulsive therapy (ECT) remains the most effective treatment to alleviate drug-refractory depression, however the neurobiological mechanisms are mostly unknown. The serotonergic system plays an important role in depression and alterations in the serotonin transporter (SERT) are seen both in depression and response to antidepressant pharmacotherapies. The first aim of this study was to investigate SERT density in a genetic rat model of depression, Flinders Sensitive Line (FSL), compared to control Flinders Resistant Line (FRL) and Sprague-Dawley (SD) rats. The second aim was to investigate SERT density in response to electroconvulsive stimuli (ECS), an animal model of ECT. Female rats of each strain were treated with ECS or sham (ear-clip placement with no current) for 10 days before brains were removed, frozen and cut into 20 µm thick sections. SERT density was measured in striatal and cortical regions by quantitative in vitro autoradiography using the SERT-radioligand, [3H]-DASB. Higher SERT density was observed in FSL rats compared to SD rats by 36–48% in motor cortex and striatum under sham conditions. In response to ECS, SD rats displayed a significant effect of treatment, whereas no changes were observed in FRL and FSL rats. Increased SERT binding in FSL rats compared to SD supports a dysfunction of the serotonergic system in depression. The increased SERT density after ECS, seen in SD rats but not FSL rats, suggests a different mechanism of action between depressive-like rats and controls.</description><subject>Autoradiography</subject><subject>DASB</subject><subject>Electroconvulsive therapy</subject><subject>Flinders resistant line rats</subject><subject>Flinders sensitive line rats</subject><subject>Serotonin transporter</subject><issn>0924-977X</issn><issn>1873-7862</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNqFUcuO2yAURVVHTebxCy3LbuwCNsYso6jTGSlSNzPS7BCB6xGRDS7gSP2A_ndJM5NtN6B7dR665yD0hZKaEtp9O9SwxOBPT80IlTVhNSHyA1rTXjSV6Dv2Ea2JZG0lhXhZoeuUDoRQ3jTyE1o1pGcd5d0a_dmGmJ3RI9be4pSj07kMCWLIwTuPc9Q-zQUEEe-dt86_4rLW-BU8FCaOOuMpWBhxGLCFOUJKLvh_egVYxjn4BDgHDCOYHIMJ_riMyR2hGLppGd0tuhr0mODu7b9Bz_ffn7YP1e7nj8ftZleZRtBcCd4y2VMpKOdMUGqHjuk958ZKxhqwXArbt6K1tKVlZWBorZai1T0HYoVobtDXs-4cw68FUlaTSwbGUXsIS1KspCeLNG8LVJyhJoaUIgxqjm7S8beiRJ06UAd16UCdOlCEqdJBYX5-M1n2E9gL7z30AticAVBOPTqIKhkH3oB1sQSkbHD_NfkL0ZyfwA</recordid><startdate>201904</startdate><enddate>201904</enddate><creator>Hvilsom, Anna Sophie Thue</creator><creator>Lillethorup, Thea P.</creator><creator>Iversen, Peter</creator><creator>Doudet, Doris J.</creator><creator>Wegener, Gregers</creator><creator>Landau, Anne M.</creator><general>Elsevier B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-7371-8713</orcidid></search><sort><creationdate>201904</creationdate><title>Cortical and striatal serotonin transporter binding in a genetic rat model of depression and in response to electroconvulsive stimuli</title><author>Hvilsom, Anna Sophie Thue ; Lillethorup, Thea P. ; Iversen, Peter ; Doudet, Doris J. ; Wegener, Gregers ; Landau, Anne M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c371t-7542981971552711df62ab55cd9223ed597d8474d141d92cef4da974a85e0d773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Autoradiography</topic><topic>DASB</topic><topic>Electroconvulsive therapy</topic><topic>Flinders resistant line rats</topic><topic>Flinders sensitive line rats</topic><topic>Serotonin transporter</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hvilsom, Anna Sophie Thue</creatorcontrib><creatorcontrib>Lillethorup, Thea P.</creatorcontrib><creatorcontrib>Iversen, Peter</creatorcontrib><creatorcontrib>Doudet, Doris J.</creatorcontrib><creatorcontrib>Wegener, Gregers</creatorcontrib><creatorcontrib>Landau, Anne M.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European neuropsychopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hvilsom, Anna Sophie Thue</au><au>Lillethorup, Thea P.</au><au>Iversen, Peter</au><au>Doudet, Doris J.</au><au>Wegener, Gregers</au><au>Landau, Anne M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cortical and striatal serotonin transporter binding in a genetic rat model of depression and in response to electroconvulsive stimuli</atitle><jtitle>European neuropsychopharmacology</jtitle><addtitle>Eur Neuropsychopharmacol</addtitle><date>2019-04</date><risdate>2019</risdate><volume>29</volume><issue>4</issue><spage>493</spage><epage>500</epage><pages>493-500</pages><issn>0924-977X</issn><eissn>1873-7862</eissn><abstract>•FSL-depressive rats and control rats were sham-handled or treated with ECS.•SERT density studied in cortex and striatum by quantitative in vitro autoradiography.•FSL rats had higher SERT density than SD control rats under sham conditions.•SD control rats, but not FSL rats, displayed a significant effect of ECS treatment.•Data support altered SERT in depression and differential strain-related ECS responses.
Depression is a debilitating mental illness and two thirds of patients respond insufficiently to conventional antidepressants. Electroconvulsive therapy (ECT) remains the most effective treatment to alleviate drug-refractory depression, however the neurobiological mechanisms are mostly unknown. The serotonergic system plays an important role in depression and alterations in the serotonin transporter (SERT) are seen both in depression and response to antidepressant pharmacotherapies. The first aim of this study was to investigate SERT density in a genetic rat model of depression, Flinders Sensitive Line (FSL), compared to control Flinders Resistant Line (FRL) and Sprague-Dawley (SD) rats. The second aim was to investigate SERT density in response to electroconvulsive stimuli (ECS), an animal model of ECT. Female rats of each strain were treated with ECS or sham (ear-clip placement with no current) for 10 days before brains were removed, frozen and cut into 20 µm thick sections. SERT density was measured in striatal and cortical regions by quantitative in vitro autoradiography using the SERT-radioligand, [3H]-DASB. Higher SERT density was observed in FSL rats compared to SD rats by 36–48% in motor cortex and striatum under sham conditions. In response to ECS, SD rats displayed a significant effect of treatment, whereas no changes were observed in FRL and FSL rats. Increased SERT binding in FSL rats compared to SD supports a dysfunction of the serotonergic system in depression. The increased SERT density after ECS, seen in SD rats but not FSL rats, suggests a different mechanism of action between depressive-like rats and controls.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>30826156</pmid><doi>10.1016/j.euroneuro.2019.02.009</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-7371-8713</orcidid></addata></record> |
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| subjects | Autoradiography DASB Electroconvulsive therapy Flinders resistant line rats Flinders sensitive line rats Serotonin transporter |
| title | Cortical and striatal serotonin transporter binding in a genetic rat model of depression and in response to electroconvulsive stimuli |
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