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Repeated exposure to ketamine in adolescent rats results in persistent anxiety in the adulthood

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Resumo:Adolescent development of the prefrontal cortex (PFC) is accompanied by important changes in glutamatergic, GABAergic and dopaminergic circuitries, susceptible to modulation by N-methyl-D-aspartate receptors (NMDAR) antagonists. Repeated ketamine was associated with social and memory deficits, but other relevant factors, such as anxiety, were not sufficiently addressed. The present study aimed to examine the behavioral and molecular consequences of repeated exposure to ketamine with a particular focus in anxiety. Methods. We treated male adolescent Wistar rats, starting postnatal day (PND) 35, with ketamine (30 mg/kg, i.p, 7 days). Behavioral evaluation was conducted in the adulthood (PND 60). The elevated plus maze (EPM) and open field tests were used to evaluate anxiety and locomotion, while sociability and novelty recognition were assessed through the novel object recognition (NOR) and the sociability and social novelty tests. At the end of the behavioral evaluation, brains were dissected and the prefrontal cortex used for biochemical evaluation. Results. Analysis of the elevated plus maze (EPM) data revealed a ketamine-induced anxiety-like profile, corroborated by the open field data. Ketaminetreated rats also failed to increase contact time with a conspecific in the social affiliation test and with an unknown rat in the novelty preference test. At the molecular level, frontal expression levels of tyrosine hydroxylase were found decreased. Conclusion. Altogether, these results show that repeated ketamine-exposure in the adolescent may result in long-term anxiety
Autores principais:Amorim, Manuela
Outros Autores:Bravo, Joana; Silva, Ana Isabel; Alves, Cecí­lia Juliana; Monteiro, Pedro; Magalhãess, Ana; Summavielle, Teresa
Assunto:Ketamine NMDAR Adolescent Anxiety Schizophrenia Prefrontal cortex
Ano:2018
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso aberto
Instituição associada:Instituto Politécnico do Porto
Idioma:inglês
Origem:Repositório Científico do Instituto Politécnico do Porto
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author Amorim, Manuela
author2 Bravo, Joana
Silva, Ana Isabel
Alves, Cecí­lia Juliana
Monteiro, Pedro
Magalhãess, Ana
Summavielle, Teresa
author2_role author
author
author
author
author
author
author_facet Amorim, Manuela
Bravo, Joana
Silva, Ana Isabel
Alves, Cecí­lia Juliana
Monteiro, Pedro
Magalhãess, Ana
Summavielle, Teresa
author_role author
contributor_name_str_mv REPOSITÓRIO P.PORTO
country_str PT
creators_json_txt [{\"Person.name\":\"Amorim, Manuela\",\"Person.identifier.orcid\":\"0009-0006-1887-4840\"},{\"Person.name\":\"Bravo, Joana\"},{\"Person.name\":\"Silva, Ana Isabel\"},{\"Person.name\":\"Alves, Cecí­lia Juliana\"},{\"Person.name\":\"Monteiro, Pedro\",\"Person.identifier.orcid\":\"0000-0002-3991-9191\"},{\"Person.name\":\"Magalhãess, Ana\"},{\"Person.name\":\"Summavielle, Teresa\",\"Person.identifier.orcid\":\"0000-0003-2548-6281\"}]
datacite.contributors.contributor.contributorName.fl_str_mv REPOSITÓRIO P.PORTO
datacite.creators.creator.creatorName.fl_str_mv Amorim, Manuela
Bravo, Joana
Silva, Ana Isabel
Alves, Cecí­lia Juliana
Monteiro, Pedro
Magalhãess, Ana
Summavielle, Teresa
datacite.date.Accepted.fl_str_mv 2018-01-01T00:00:00Z
datacite.date.available.fl_str_mv 2020-09-14T10:54:55Z
datacite.date.embargoed.fl_str_mv 2020-09-14T10:54:55Z
datacite.rights.fl_str_mv http://purl.org/coar/access_right/c_abf2
datacite.subjects.subject.fl_str_mv Ketamine
NMDAR
Adolescent
Anxiety
Schizophrenia
Prefrontal cortex
datacite.titles.title.fl_str_mv Repeated exposure to ketamine in adolescent rats results in persistent anxiety in the adulthood
dc.contributor.none.fl_str_mv REPOSITÓRIO P.PORTO
dc.creator.none.fl_str_mv Amorim, Manuela
Bravo, Joana
Silva, Ana Isabel
Alves, Cecí­lia Juliana
Monteiro, Pedro
Magalhãess, Ana
Summavielle, Teresa
dc.date.Accepted.fl_str_mv 2018-01-01T00:00:00Z
dc.date.available.fl_str_mv 2020-09-14T10:54:55Z
dc.date.embargoed.fl_str_mv 2020-09-14T10:54:55Z
dc.format.none.fl_str_mv application/pdf
dc.identifier.none.fl_str_mv http://hdl.handle.net/10400.22/16251
dc.language.none.fl_str_mv eng
dc.publisher.none.fl_str_mv Ashdin Publishing
dc.rights.none.fl_str_mv http://purl.org/coar/access_right/c_abf2
dc.subject.none.fl_str_mv Ketamine
NMDAR
Adolescent
Anxiety
Schizophrenia
Prefrontal cortex
dc.title.fl_str_mv Repeated exposure to ketamine in adolescent rats results in persistent anxiety in the adulthood
dc.type.none.fl_str_mv http://purl.org/coar/resource_type/c_6501
description Adolescent development of the prefrontal cortex (PFC) is accompanied by important changes in glutamatergic, GABAergic and dopaminergic circuitries, susceptible to modulation by N-methyl-D-aspartate receptors (NMDAR) antagonists. Repeated ketamine was associated with social and memory deficits, but other relevant factors, such as anxiety, were not sufficiently addressed. The present study aimed to examine the behavioral and molecular consequences of repeated exposure to ketamine with a particular focus in anxiety. Methods. We treated male adolescent Wistar rats, starting postnatal day (PND) 35, with ketamine (30 mg/kg, i.p, 7 days). Behavioral evaluation was conducted in the adulthood (PND 60). The elevated plus maze (EPM) and open field tests were used to evaluate anxiety and locomotion, while sociability and novelty recognition were assessed through the novel object recognition (NOR) and the sociability and social novelty tests. At the end of the behavioral evaluation, brains were dissected and the prefrontal cortex used for biochemical evaluation. Results. Analysis of the elevated plus maze (EPM) data revealed a ketamine-induced anxiety-like profile, corroborated by the open field data. Ketaminetreated rats also failed to increase contact time with a conspecific in the social affiliation test and with an unknown rat in the novelty preference test. At the molecular level, frontal expression levels of tyrosine hydroxylase were found decreased. Conclusion. Altogether, these results show that repeated ketamine-exposure in the adolescent may result in long-term anxiety
dirty 0
eu_rights_str_mv openAccess
format article
fulltext.url.fl_str_mv https://recipp.ipp.pt/bitstreams/e6006ba3-4c9a-46da-b5d3-03499f2ff7da/download
id recipp_bc8e7c809cfdfcfef61a67ece407f522
identifier.url.fl_str_mv http://hdl.handle.net/10400.22/16251
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institution Instituto Politécnico do Porto
instname_str Instituto Politécnico do Porto
language eng
network_acronym_str recipp
network_name_str Repositório Científico do Instituto Politécnico do Porto
oai_identifier_str oai:recipp.ipp.pt:10400.22/16251
organization_str_mv urn:organizationAcronym:recipp
person_str_mv Amorim, Manuela
Amorim, Manuela
https://www.ciencia-id.pt/CD1D-1B47-A971
CD1D-1B47-A971
http://orcid.org/0009-0006-1887-4840
0009-0006-1887-4840
Bravo, Joana
Silva, Ana Isabel
Alves, Cecí­lia Juliana
Monteiro, Pedro
Monteiro, Pedro
https://www.ciencia-id.pt/2414-4468-928B
2414-4468-928B
http://orcid.org/0000-0002-3991-9191
0000-0002-3991-9191
Magalhãess, Ana
Summavielle, Teresa
Summavielle, Teresa
https://www.ciencia-id.pt/C41E-0816-5C85
C41E-0816-5C85
http://orcid.org/0000-0003-2548-6281
0000-0003-2548-6281
publishDate 2018
publisher.none.fl_str_mv Ashdin Publishing
reponame_str Repositório Científico do Instituto Politécnico do Porto
repository_id_str urn:repositoryAcronym:recipp
service_str_mv urn:repositoryAcronym:recipp
spelling engAshdin Publishingpt_PTAdolescent development of the prefrontal cortex (PFC) is accompanied by important changes in glutamatergic, GABAergic and dopaminergic circuitries, susceptible to modulation by N-methyl-D-aspartate receptors (NMDAR) antagonists. Repeated ketamine was associated with social and memory deficits, but other relevant factors, such as anxiety, were not sufficiently addressed. The present study aimed to examine the behavioral and molecular consequences of repeated exposure to ketamine with a particular focus in anxiety. Methods. We treated male adolescent Wistar rats, starting postnatal day (PND) 35, with ketamine (30 mg/kg, i.p, 7 days). Behavioral evaluation was conducted in the adulthood (PND 60). The elevated plus maze (EPM) and open field tests were used to evaluate anxiety and locomotion, while sociability and novelty recognition were assessed through the novel object recognition (NOR) and the sociability and social novelty tests. At the end of the behavioral evaluation, brains were dissected and the prefrontal cortex used for biochemical evaluation. Results. Analysis of the elevated plus maze (EPM) data revealed a ketamine-induced anxiety-like profile, corroborated by the open field data. Ketaminetreated rats also failed to increase contact time with a conspecific in the social affiliation test and with an unknown rat in the novelty preference test. At the molecular level, frontal expression levels of tyrosine hydroxylase were found decreased. Conclusion. Altogether, these results show that repeated ketamine-exposure in the adolescent may result in long-term anxietyapplication/pdfpt_PTRepeated exposure to ketamine in adolescent rats results in persistent anxiety in the adulthoodPersonalAmorim, ManuelaDSpacehttp://dspace.org/items/10df22ed-9823-452e-89a8-8cbe89e717ecDSpacehttp://dspace.org/items/10df22ed-9823-452e-89a8-8cbe89e717ecAmorim SousaMaria ManuelaCiência IDhttps://www.ciencia-id.ptCD1D-1B47-A971ORCIDhttp://orcid.org0009-0006-1887-4840Bravo, JoanaSilva, Ana IsabelAlves, Cecí­lia JulianaPersonalMonteiro, PedroDSpacehttp://dspace.org/items/fae8b5b3-db39-4d56-a2b1-2db0388279b9DSpacehttp://dspace.org/items/fae8b5b3-db39-4d56-a2b1-2db0388279b9MonteiroPedroCiência IDhttps://www.ciencia-id.pt2414-4468-928BORCIDhttp://orcid.org0000-0002-3991-9191Scopus Author IDhttps://www.scopus.com6504494827Scopus Author IDhttps://www.scopus.com57192572968Magalhãess, AnaPersonalSummavielle, TeresaDSpacehttp://dspace.org/items/207ee2de-85a0-4144-9e7e-b376c600e065DSpacehttp://dspace.org/items/207ee2de-85a0-4144-9e7e-b376c600e065SummavielleTeresaCiência IDhttps://www.ciencia-id.ptC41E-0816-5C85ORCIDhttp://orcid.org0000-0003-2548-6281Researcher IDhttps://www.researcherid.comC-9776-2012Scopus Author IDhttps://www.scopus.com6603092949HostingInstitutionOrganizationalREPOSITÓRIO P.PORTOe-mailmailto:recipp@sc.ipp.ptrecipp@sc.ipp.ptDOIIsPartOf10.4303/jdar/2360602020-09-14T10:54:55Z20182018-01-01T00:00:00ZHandlehttp://hdl.handle.net/10400.22/16251http://purl.org/coar/access_right/c_abf2open accessKetamineNMDARAdolescentAnxietySchizophreniaPrefrontal cortex1132789 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://recipp.ipp.pt/bitstreams/e6006ba3-4c9a-46da-b5d3-03499f2ff7da/downloadJournal of drug and alcohol research0701
spellingShingle Repeated exposure to ketamine in adolescent rats results in persistent anxiety in the adulthood
Amorim, Manuela
Ketamine
NMDAR
Adolescent
Anxiety
Schizophrenia
Prefrontal cortex
status SINGLETON
subject.fl_str_mv Ketamine
NMDAR
Adolescent
Anxiety
Schizophrenia
Prefrontal cortex
title Repeated exposure to ketamine in adolescent rats results in persistent anxiety in the adulthood
title_full Repeated exposure to ketamine in adolescent rats results in persistent anxiety in the adulthood
title_fullStr Repeated exposure to ketamine in adolescent rats results in persistent anxiety in the adulthood
title_full_unstemmed Repeated exposure to ketamine in adolescent rats results in persistent anxiety in the adulthood
title_short Repeated exposure to ketamine in adolescent rats results in persistent anxiety in the adulthood
title_sort Repeated exposure to ketamine in adolescent rats results in persistent anxiety in the adulthood
topic Ketamine
NMDAR
Adolescent
Anxiety
Schizophrenia
Prefrontal cortex
topic_facet Ketamine
NMDAR
Adolescent
Anxiety
Schizophrenia
Prefrontal cortex
url http://hdl.handle.net/10400.22/16251
visible 1