Sertraline effects on cerebrospinal fluid monoamines and species-typical socioemotional behavior of female cynomolgus monkeys
Rationale Although widely prescribed, little is known about the effects of selective serotonin reuptake inhibitors (SSRIs) on social behavior and cerebrospinal fluid (CSF) monoamines in female primates. Objective The objective of this study was to determine the effects of sertraline on agonistic and...
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| Veröffentlicht in: | Psychopharmacology 2014-04, Vol.231 (7), p.1409-1416 |
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| creator | Shively, Carol A. Register, Thomas C. Higley, J. Dee Willard, Stephanie L. |
| description | Rationale
Although widely prescribed, little is known about the effects of selective serotonin reuptake inhibitors (SSRIs) on social behavior and cerebrospinal fluid (CSF) monoamines in female primates.
Objective
The objective of this study was to determine the effects of sertraline on agonistic and affiliative behavior.
Methods
Twenty-one adult female cynomolgus monkeys were housed in small, stable social groups, trained to participate in oral dosing, and began a 5-week cumulative dose–response study. Serial doses of 0, 5, 10, 15, and 20 mg/kg of sertraline were administered orally for 1 week each. Behavior was recorded daily during 10-min observations before and 4 h after dosing. On the seventh day of dosing, circulating sertraline/desmethylsertraline and CSF monoamines/metabolites were determined 4 h after the last dose.
Results
At 20 mg/kg, circulating sertraline/desmethylsertraline was in the therapeutic range. CSF 5-hydroxyindole acetic acid decreased by 33 % (
p
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| doi_str_mv | 10.1007/s00213-013-3329-9 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3954916</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A372253088</galeid><sourcerecordid>A372253088</sourcerecordid><originalsourceid>FETCH-LOGICAL-c636t-43476e0fabacdd598c0be41c13384a0f6e148d06488cbb3ab4ff59eebb9a811f3</originalsourceid><addsrcrecordid>eNp1ktFv1SAUxonRuOv0D_DFkPjiSycU2sKLybI4NVmyh81nAvRwx2yhQrvkPvi_S3fn3BYtaUg4v-8j5_Ah9JaSI0pI9zETUlNWkfIzVstKPkMbylld1aSrn6MNIaxUaCMO0Kucr0n5uOAv0UHNqWSsoxv06wLSnPTgA2BwDuyccQzYQgKTYp580AN2w-J7PMYQ9VjAjHXocZ7AesjVvJu8LVCO1kcY4-zjqjFwpW98TDg67GDUA2C7C3GMw3bJq9cP2OXX6IXTQ4Y3d_sh-n76-fLka3V2_uXbyfFZZVvWzhVnvGuBOG207ftGCksMcGopY4Jr4lqgXPSk5UJYY5g23LlGAhgjtaDUsUP0ae87LWaE3kJYe1ZT8qNOOxW1V48rwV-pbbxRTDZc0rYYfLgzSPHnAnlWo88WhkEHiEtWtCGia7qOioK-f4JexyWVkdxSLae0lfwvtS2TUT64WO61q6k6Zl1dN4yI1evoH1RZPYzexgDOl_NHAroX2PJ4OYG775EStWZG7TOjSmbUmhkli-bdw-HcK_6EpAD1HsilFLaQHnT0X9ffmh_PQA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1506411694</pqid></control><display><type>article</type><title>Sertraline effects on cerebrospinal fluid monoamines and species-typical socioemotional behavior of female cynomolgus monkeys</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Shively, Carol A. ; Register, Thomas C. ; Higley, J. Dee ; Willard, Stephanie L.</creator><creatorcontrib>Shively, Carol A. ; Register, Thomas C. ; Higley, J. Dee ; Willard, Stephanie L.</creatorcontrib><description>Rationale
Although widely prescribed, little is known about the effects of selective serotonin reuptake inhibitors (SSRIs) on social behavior and cerebrospinal fluid (CSF) monoamines in female primates.
Objective
The objective of this study was to determine the effects of sertraline on agonistic and affiliative behavior.
Methods
Twenty-one adult female cynomolgus monkeys were housed in small, stable social groups, trained to participate in oral dosing, and began a 5-week cumulative dose–response study. Serial doses of 0, 5, 10, 15, and 20 mg/kg of sertraline were administered orally for 1 week each. Behavior was recorded daily during 10-min observations before and 4 h after dosing. On the seventh day of dosing, circulating sertraline/desmethylsertraline and CSF monoamines/metabolites were determined 4 h after the last dose.
Results
At 20 mg/kg, circulating sertraline/desmethylsertraline was in the therapeutic range. CSF 5-hydroxyindole acetic acid decreased by 33 % (
p
< 0.05). Overall aggression, submission, locomotion, and time alone decreased, whereas affiliative behaviors (body contact, grooming) increased (all
p
values <0.05). Effects of sertraline on aggression and submission were social status-dependent, reducing aggression in dominants and submission in subordinates.
Conclusions
A clinically relevant oral dose of sertraline resulted in CSF metabolite changes similar to those observed in patients and altered the socioemotional behavior of female monkeys. Changes in CSF 5-HT and dopamine are novel observations that may be sex-specific. The robust effects of sertraline on aggression and affiliation may explain the efficacy of SSRIs on a range of human behavioral pathologies that share the characteristics of increased aggression and decreased sociality.</description><identifier>ISSN: 0033-3158</identifier><identifier>EISSN: 1432-2072</identifier><identifier>DOI: 10.1007/s00213-013-3329-9</identifier><identifier>PMID: 24193371</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Animals ; Behavioral biology ; Biogenic Monoamines - cerebrospinal fluid ; Biogenic Monoamines - metabolism ; Biomedical and Life Sciences ; Biomedicine ; Cerebrospinal fluid ; Circadian Rhythm - drug effects ; Complications and side effects ; Cynomolgus ; Dosage and administration ; Dose-Response Relationship, Drug ; Drug therapy ; Female ; Genetic aspects ; Hierarchy, Social ; Hydroxyindoleacetic Acid - cerebrospinal fluid ; Hydroxyindoleacetic Acid - metabolism ; Macaca fascicularis ; Neurosciences ; Original Investigation ; Pharmacology/Toxicology ; Physiological aspects ; Primates ; Psychiatry ; Psychopharmacology ; Serotonin Uptake Inhibitors - administration & dosage ; Serotonin Uptake Inhibitors - pharmacokinetics ; Serotonin Uptake Inhibitors - pharmacology ; Sertraline ; Sertraline - administration & dosage ; Sertraline - pharmacokinetics ; Sertraline - pharmacology ; Social aspects ; Social Behavior ; Social behavior in animals</subject><ispartof>Psychopharmacology, 2014-04, Vol.231 (7), p.1409-1416</ispartof><rights>Springer-Verlag Berlin Heidelberg 2013</rights><rights>COPYRIGHT 2014 Springer</rights><rights>Springer-Verlag Berlin Heidelberg 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c636t-43476e0fabacdd598c0be41c13384a0f6e148d06488cbb3ab4ff59eebb9a811f3</citedby><cites>FETCH-LOGICAL-c636t-43476e0fabacdd598c0be41c13384a0f6e148d06488cbb3ab4ff59eebb9a811f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00213-013-3329-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00213-013-3329-9$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24193371$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shively, Carol A.</creatorcontrib><creatorcontrib>Register, Thomas C.</creatorcontrib><creatorcontrib>Higley, J. Dee</creatorcontrib><creatorcontrib>Willard, Stephanie L.</creatorcontrib><title>Sertraline effects on cerebrospinal fluid monoamines and species-typical socioemotional behavior of female cynomolgus monkeys</title><title>Psychopharmacology</title><addtitle>Psychopharmacology</addtitle><addtitle>Psychopharmacology (Berl)</addtitle><description>Rationale
Although widely prescribed, little is known about the effects of selective serotonin reuptake inhibitors (SSRIs) on social behavior and cerebrospinal fluid (CSF) monoamines in female primates.
Objective
The objective of this study was to determine the effects of sertraline on agonistic and affiliative behavior.
Methods
Twenty-one adult female cynomolgus monkeys were housed in small, stable social groups, trained to participate in oral dosing, and began a 5-week cumulative dose–response study. Serial doses of 0, 5, 10, 15, and 20 mg/kg of sertraline were administered orally for 1 week each. Behavior was recorded daily during 10-min observations before and 4 h after dosing. On the seventh day of dosing, circulating sertraline/desmethylsertraline and CSF monoamines/metabolites were determined 4 h after the last dose.
Results
At 20 mg/kg, circulating sertraline/desmethylsertraline was in the therapeutic range. CSF 5-hydroxyindole acetic acid decreased by 33 % (
p
< 0.05). Overall aggression, submission, locomotion, and time alone decreased, whereas affiliative behaviors (body contact, grooming) increased (all
p
values <0.05). Effects of sertraline on aggression and submission were social status-dependent, reducing aggression in dominants and submission in subordinates.
Conclusions
A clinically relevant oral dose of sertraline resulted in CSF metabolite changes similar to those observed in patients and altered the socioemotional behavior of female monkeys. Changes in CSF 5-HT and dopamine are novel observations that may be sex-specific. The robust effects of sertraline on aggression and affiliation may explain the efficacy of SSRIs on a range of human behavioral pathologies that share the characteristics of increased aggression and decreased sociality.</description><subject>Animals</subject><subject>Behavioral biology</subject><subject>Biogenic Monoamines - cerebrospinal fluid</subject><subject>Biogenic Monoamines - metabolism</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cerebrospinal fluid</subject><subject>Circadian Rhythm - drug effects</subject><subject>Complications and side effects</subject><subject>Cynomolgus</subject><subject>Dosage and administration</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug therapy</subject><subject>Female</subject><subject>Genetic aspects</subject><subject>Hierarchy, Social</subject><subject>Hydroxyindoleacetic Acid - cerebrospinal fluid</subject><subject>Hydroxyindoleacetic Acid - metabolism</subject><subject>Macaca fascicularis</subject><subject>Neurosciences</subject><subject>Original Investigation</subject><subject>Pharmacology/Toxicology</subject><subject>Physiological aspects</subject><subject>Primates</subject><subject>Psychiatry</subject><subject>Psychopharmacology</subject><subject>Serotonin Uptake Inhibitors - administration & dosage</subject><subject>Serotonin Uptake Inhibitors - pharmacokinetics</subject><subject>Serotonin Uptake Inhibitors - pharmacology</subject><subject>Sertraline</subject><subject>Sertraline - administration & dosage</subject><subject>Sertraline - pharmacokinetics</subject><subject>Sertraline - pharmacology</subject><subject>Social aspects</subject><subject>Social Behavior</subject><subject>Social behavior in animals</subject><issn>0033-3158</issn><issn>1432-2072</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1ktFv1SAUxonRuOv0D_DFkPjiSycU2sKLybI4NVmyh81nAvRwx2yhQrvkPvi_S3fn3BYtaUg4v-8j5_Ah9JaSI0pI9zETUlNWkfIzVstKPkMbylld1aSrn6MNIaxUaCMO0Kucr0n5uOAv0UHNqWSsoxv06wLSnPTgA2BwDuyccQzYQgKTYp580AN2w-J7PMYQ9VjAjHXocZ7AesjVvJu8LVCO1kcY4-zjqjFwpW98TDg67GDUA2C7C3GMw3bJq9cP2OXX6IXTQ4Y3d_sh-n76-fLka3V2_uXbyfFZZVvWzhVnvGuBOG207ftGCksMcGopY4Jr4lqgXPSk5UJYY5g23LlGAhgjtaDUsUP0ae87LWaE3kJYe1ZT8qNOOxW1V48rwV-pbbxRTDZc0rYYfLgzSPHnAnlWo88WhkEHiEtWtCGia7qOioK-f4JexyWVkdxSLae0lfwvtS2TUT64WO61q6k6Zl1dN4yI1evoH1RZPYzexgDOl_NHAroX2PJ4OYG775EStWZG7TOjSmbUmhkli-bdw-HcK_6EpAD1HsilFLaQHnT0X9ffmh_PQA</recordid><startdate>20140401</startdate><enddate>20140401</enddate><creator>Shively, Carol A.</creator><creator>Register, Thomas C.</creator><creator>Higley, J. Dee</creator><creator>Willard, Stephanie L.</creator><general>Springer Berlin Heidelberg</general><general>Springer</general><general>Springer Nature B.V</general><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>3V.</scope><scope>7QG</scope><scope>7QR</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>5PM</scope></search><sort><creationdate>20140401</creationdate><title>Sertraline effects on cerebrospinal fluid monoamines and species-typical socioemotional behavior of female cynomolgus monkeys</title><author>Shively, Carol A. ; Register, Thomas C. ; Higley, J. Dee ; Willard, Stephanie L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c636t-43476e0fabacdd598c0be41c13384a0f6e148d06488cbb3ab4ff59eebb9a811f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Behavioral biology</topic><topic>Biogenic Monoamines - cerebrospinal fluid</topic><topic>Biogenic Monoamines - metabolism</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cerebrospinal fluid</topic><topic>Circadian Rhythm - drug effects</topic><topic>Complications and side effects</topic><topic>Cynomolgus</topic><topic>Dosage and administration</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug therapy</topic><topic>Female</topic><topic>Genetic aspects</topic><topic>Hierarchy, Social</topic><topic>Hydroxyindoleacetic Acid - cerebrospinal fluid</topic><topic>Hydroxyindoleacetic Acid - metabolism</topic><topic>Macaca fascicularis</topic><topic>Neurosciences</topic><topic>Original Investigation</topic><topic>Pharmacology/Toxicology</topic><topic>Physiological aspects</topic><topic>Primates</topic><topic>Psychiatry</topic><topic>Psychopharmacology</topic><topic>Serotonin Uptake Inhibitors - administration & dosage</topic><topic>Serotonin Uptake Inhibitors - pharmacokinetics</topic><topic>Serotonin Uptake Inhibitors - pharmacology</topic><topic>Sertraline</topic><topic>Sertraline - administration & dosage</topic><topic>Sertraline - pharmacokinetics</topic><topic>Sertraline - pharmacology</topic><topic>Social aspects</topic><topic>Social Behavior</topic><topic>Social behavior in animals</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shively, Carol A.</creatorcontrib><creatorcontrib>Register, Thomas C.</creatorcontrib><creatorcontrib>Higley, J. Dee</creatorcontrib><creatorcontrib>Willard, Stephanie L.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Psychopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shively, Carol A.</au><au>Register, Thomas C.</au><au>Higley, J. Dee</au><au>Willard, Stephanie L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sertraline effects on cerebrospinal fluid monoamines and species-typical socioemotional behavior of female cynomolgus monkeys</atitle><jtitle>Psychopharmacology</jtitle><stitle>Psychopharmacology</stitle><addtitle>Psychopharmacology (Berl)</addtitle><date>2014-04-01</date><risdate>2014</risdate><volume>231</volume><issue>7</issue><spage>1409</spage><epage>1416</epage><pages>1409-1416</pages><issn>0033-3158</issn><eissn>1432-2072</eissn><abstract>Rationale
Although widely prescribed, little is known about the effects of selective serotonin reuptake inhibitors (SSRIs) on social behavior and cerebrospinal fluid (CSF) monoamines in female primates.
Objective
The objective of this study was to determine the effects of sertraline on agonistic and affiliative behavior.
Methods
Twenty-one adult female cynomolgus monkeys were housed in small, stable social groups, trained to participate in oral dosing, and began a 5-week cumulative dose–response study. Serial doses of 0, 5, 10, 15, and 20 mg/kg of sertraline were administered orally for 1 week each. Behavior was recorded daily during 10-min observations before and 4 h after dosing. On the seventh day of dosing, circulating sertraline/desmethylsertraline and CSF monoamines/metabolites were determined 4 h after the last dose.
Results
At 20 mg/kg, circulating sertraline/desmethylsertraline was in the therapeutic range. CSF 5-hydroxyindole acetic acid decreased by 33 % (
p
< 0.05). Overall aggression, submission, locomotion, and time alone decreased, whereas affiliative behaviors (body contact, grooming) increased (all
p
values <0.05). Effects of sertraline on aggression and submission were social status-dependent, reducing aggression in dominants and submission in subordinates.
Conclusions
A clinically relevant oral dose of sertraline resulted in CSF metabolite changes similar to those observed in patients and altered the socioemotional behavior of female monkeys. Changes in CSF 5-HT and dopamine are novel observations that may be sex-specific. The robust effects of sertraline on aggression and affiliation may explain the efficacy of SSRIs on a range of human behavioral pathologies that share the characteristics of increased aggression and decreased sociality.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>24193371</pmid><doi>10.1007/s00213-013-3329-9</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0033-3158 |
| ispartof | Psychopharmacology, 2014-04, Vol.231 (7), p.1409-1416 |
| issn | 0033-3158 1432-2072 |
| language | eng |
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| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Animals Behavioral biology Biogenic Monoamines - cerebrospinal fluid Biogenic Monoamines - metabolism Biomedical and Life Sciences Biomedicine Cerebrospinal fluid Circadian Rhythm - drug effects Complications and side effects Cynomolgus Dosage and administration Dose-Response Relationship, Drug Drug therapy Female Genetic aspects Hierarchy, Social Hydroxyindoleacetic Acid - cerebrospinal fluid Hydroxyindoleacetic Acid - metabolism Macaca fascicularis Neurosciences Original Investigation Pharmacology/Toxicology Physiological aspects Primates Psychiatry Psychopharmacology Serotonin Uptake Inhibitors - administration & dosage Serotonin Uptake Inhibitors - pharmacokinetics Serotonin Uptake Inhibitors - pharmacology Sertraline Sertraline - administration & dosage Sertraline - pharmacokinetics Sertraline - pharmacology Social aspects Social Behavior Social behavior in animals |
| title | Sertraline effects on cerebrospinal fluid monoamines and species-typical socioemotional behavior of female cynomolgus monkeys |
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