O sistema opioide contribui para o efeito do tipo antidepressivo do disseleneto de m-trifluormetil-difenila em camundongos
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional Manancial UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/14934 |
Resumo: | Depression is a mental disorder with complex pathophysiology and characterized by multiple symptoms, which makes it difficult to treat this disease. In the last decades, the opioid system has become the focus of depression researches, given that this system has an important regulatory effect on mood. However, the opioids use in the clinic is limited by the development of tolerance and dependence after repeated administration. The organoselenium compound m-trifluoromethyl-diphenyl diselenide (m-CF3-PhSe)2 elicits antidepressant-like effect in animal models through different action targets, including the opioid system. Thus, the main objective of this thesis was to evaluate the opioid system contribution to the pharmacological effect of the organic compound of selenium (m-CF3-PhSe)2 in models of depression in swiss male mice. The results of article 1 demonstrated the (m-CF3-PhSe)2 antidepressant-like effect on the forced swimming test (FST) and the contribution of each opioid receptor to this effect through the use of selective antagonists of these receptors, suggesting that μ and δ receptors activation and κ-receptor blockade are involved in the antidepressant-like action of the compound. In addition, article 1 revealed the antidepressant-like effect of acute or repeated administration of (m-CF3-PhSe)2 on the FST and the modified tail suspension test (TST). In the modified TST, the involvement of the opioid system in the antidepressant-like action of the compound was demonstrated by the increase of behaviors characteristic of opioid system modulation. The article 1 also demonstrated that repeated administration of (m-CF3-PhSe)2 neither induce tolerance in the FST nor physical signs of naloxone-induced withdrawal and did not alter systemic toxicity parameters. Based on these results, it was investigated the molecular mechanisms by which the opioid system contributes to the antidepressant-like effect of (m- CF3-PhSe)2. For this, stress-induced depression models were carried out, given that the opioid system is involved in the different responses to stress. The article 2 revealed that one or repeated forced swimming stress (FSS) exposures induced depressant-like behavior and affected the prefrontal cortical opioid receptor levels of mice. In this study, (m-CF3-PhSe)2 was effective against depressant-like symptoms induced by repeated FSS in the FST, the TST and the splash test through of μ and κ receptor levels regulation. Therefore, the (m-CF3- PhSe)2 effect was investigated in a more severe and prolonged stress model in the article 3. In this study, social defeat stress (SDS) induced social aversion and altered the levels of the three opioid receptors types in the prefrontal cortex of susceptible mice. (m-CF3-PhSe)2 was effective against these changes, promoting resilience to SDS and increasing the natural sociability among mice. Together, the results of this thesis contributes to the understanding of the opioid mechanisms involved in the antidepressant-like effect of (m-CF3-PhSe)2 and indicates that this compound may be an therapeutic alternative for the treatment of depression. |
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2018-11-26T13:06:47Z2018-11-26T13:06:47Z2018-07-20http://repositorio.ufsm.br/handle/1/14934Depression is a mental disorder with complex pathophysiology and characterized by multiple symptoms, which makes it difficult to treat this disease. In the last decades, the opioid system has become the focus of depression researches, given that this system has an important regulatory effect on mood. However, the opioids use in the clinic is limited by the development of tolerance and dependence after repeated administration. The organoselenium compound m-trifluoromethyl-diphenyl diselenide (m-CF3-PhSe)2 elicits antidepressant-like effect in animal models through different action targets, including the opioid system. Thus, the main objective of this thesis was to evaluate the opioid system contribution to the pharmacological effect of the organic compound of selenium (m-CF3-PhSe)2 in models of depression in swiss male mice. The results of article 1 demonstrated the (m-CF3-PhSe)2 antidepressant-like effect on the forced swimming test (FST) and the contribution of each opioid receptor to this effect through the use of selective antagonists of these receptors, suggesting that μ and δ receptors activation and κ-receptor blockade are involved in the antidepressant-like action of the compound. In addition, article 1 revealed the antidepressant-like effect of acute or repeated administration of (m-CF3-PhSe)2 on the FST and the modified tail suspension test (TST). In the modified TST, the involvement of the opioid system in the antidepressant-like action of the compound was demonstrated by the increase of behaviors characteristic of opioid system modulation. The article 1 also demonstrated that repeated administration of (m-CF3-PhSe)2 neither induce tolerance in the FST nor physical signs of naloxone-induced withdrawal and did not alter systemic toxicity parameters. Based on these results, it was investigated the molecular mechanisms by which the opioid system contributes to the antidepressant-like effect of (m- CF3-PhSe)2. For this, stress-induced depression models were carried out, given that the opioid system is involved in the different responses to stress. The article 2 revealed that one or repeated forced swimming stress (FSS) exposures induced depressant-like behavior and affected the prefrontal cortical opioid receptor levels of mice. In this study, (m-CF3-PhSe)2 was effective against depressant-like symptoms induced by repeated FSS in the FST, the TST and the splash test through of μ and κ receptor levels regulation. Therefore, the (m-CF3- PhSe)2 effect was investigated in a more severe and prolonged stress model in the article 3. In this study, social defeat stress (SDS) induced social aversion and altered the levels of the three opioid receptors types in the prefrontal cortex of susceptible mice. (m-CF3-PhSe)2 was effective against these changes, promoting resilience to SDS and increasing the natural sociability among mice. Together, the results of this thesis contributes to the understanding of the opioid mechanisms involved in the antidepressant-like effect of (m-CF3-PhSe)2 and indicates that this compound may be an therapeutic alternative for the treatment of depression.A depressão é um transtorno mental de patofisiologia complexa e caracterizada por múltiplos sintomas, o que dificulta o tratamento desta doença. Nas últimas décadas, o sistema opioide tornou-se foco de pesquisas sobre a depressão, uma vez que este sistema exerce um importante efeito regulatório sobre o humor. No entanto, o uso de opioides na clínica é limitado pelo desenvolvimento de tolerância e dependência após a administração repetida. O composto orgânico de selênio disseleneto de m-trifluormetil-difenila (m-CF3-PhSe)2 apresenta efeito do tipo antidepressivo em modelos animais por meio de diferentes alvos de ação, que incluem o sistema opioide. Assim, o principal objetivo desta tese foi avaliar a contribuição do sistema opioide para o efeito farmacológico do composto orgânico de selênio (m-CF3-PhSe)2 em modelos de depressão em camundongos Swiss machos. Os resultados do artigo 1 demostraram o efeito do tipo antidepressivo do (m- CF3-PhSe)2 no teste do nado forçado (TNF) e a contribuição de cada receptor opioide para este efeito, por meio do uso de antagonistas seletivos destes receptores, sugerindo que a ativação de receptores μ e δ e o bloqueio dos receptores κ estão envolvidos na ação do tipo antidepressiva do composto. Além disso, o artigo 1 revelou o efeito do tipo antidepressivo da administração aguda ou repetida do (m-CF3-PhSe) no TNF e teste de suspensão da cauda (TSC) modificado. Neste último, o envolvimento do sistema opioide na ação do tipo antidepressiva do composto foi evidenciado por meio do aumento de comportamentos característicos da modulação do sistema opioide. O artigo 1 também demonstrou que a administração repetida do (m-CF3-PhSe)2 não induz tolerância no TNF e sinais físicos de abstinência induzidos por naloxona e não altera parâmetros de toxicidade sistêmica. Com base nestes resultados, buscou-se investigar mecanismos moleculares pelos quais o sistema opioide contribui para os efeitos do tipo antidepressivo do (m-CF3-PhSe)2. Para isso, modelos de depressão induzidas por estresse foram utilizados, uma vez que o sistema opioide está envolvido nas diferentes respostas ao estresse. No artigo 2, o efeito de uma ou repetidas exposições ao estresse de natação forçada (ENF) sobre o comportamento do tipo depressivo e nos níveis de receptores opioides em córtex pré-frontal de camundongos foi demonstrada. Neste estudo, o (m-CF3-PhSe)2 foi efetivo contra os sintomas do tipo depressivos no TNF, TSC e splash teste induzidos pelo ENF repetido por meio da regulação dos níveis de receptores μ e κ. Portanto, o efeito do (m-CF3-PhSe)2 foi investigado em um modelo de estresse mais severo e prolongado no artigo 3. Neste estudo, o estresse de derrota social (EDS) induziu aversão social e alterou os níveis dos três tipos de receptores opioides em córtex pré-frontal de camundongos suscetíveis. Além disso, o (m-CF3-PhSe)2 foi efetivo contra estas alterações promovendo resiliência ao EDS, além de aumentar a sociabilidade natural entre os camundongos. Em conjunto, os resultados desta tese contribuem para a compreensão dos mecanismos opioides envolvidos no efeito do tipo antidepressivo do (m-CF3-PhSe)2 e indicam que este composto pode ser uma alternativa terapêutica para o tratamento da depressão.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade Federal de Santa MariaCentro de Ciências Naturais e ExatasPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaUFSMBrasilBioquímicaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessDepressãoSelênioSistema opioideEstresseDepressionSeleniumOpioid systemStressCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAO sistema opioide contribui para o efeito do tipo antidepressivo do disseleneto de m-trifluormetil-difenila em camundongosOpioid system contributes to m-trifluoromethyl-diphenyl diselenide antidepressant-like efect in miceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisNogueira, Cristina Waynehttp://lattes.cnpq.br/2877042401245169Torres, Iraci Lucena da Silvahttp://lattes.cnpq.br/3765572633415830Franco, Jeferson Luishttp://lattes.cnpq.br/1680065573338339Prigol, Marinahttp://lattes.cnpq.br/6724052141066150Oliveira, Mauro Schneiderhttp://lattes.cnpq.br/7132934163734175http://lattes.cnpq.br/4191126676996771Rosa, Suzan Gonçalves2008000000026000186436d-f662-4a5e-b36e-8c8ab8e10bf8540c8d5c-599c-43b3-9c3e-856d343615570655425f-8473-4bd2-90c1-fe1150c7d80b423a65fa-1ad8-43d9-b50e-5041a255d6a0a641ed0f-fe45-4199-9dff-bfcbfed1ee56bc6a3080-3417-4388-91eb-a617cab7964dreponame:Repositório Institucional Manancial UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALTES_PPGCBBT_2018_ROSA_SUZAN.pdfTES_PPGCBBT_2018_ROSA_SUZAN.pdfTese de Doutoradoapplication/pdf21046688http://repositorio.ufsm.br/bitstream/1/14934/1/TES_PPGCBBT_2018_ROSA_SUZAN.pdf60d2c8514e7d583ed4ffec831b7d341cMD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
O sistema opioide contribui para o efeito do tipo antidepressivo do disseleneto de m-trifluormetil-difenila em camundongos |
dc.title.alternative.eng.fl_str_mv |
Opioid system contributes to m-trifluoromethyl-diphenyl diselenide antidepressant-like efect in mice |
title |
O sistema opioide contribui para o efeito do tipo antidepressivo do disseleneto de m-trifluormetil-difenila em camundongos |
spellingShingle |
O sistema opioide contribui para o efeito do tipo antidepressivo do disseleneto de m-trifluormetil-difenila em camundongos Rosa, Suzan Gonçalves Depressão Selênio Sistema opioide Estresse Depression Selenium Opioid system Stress CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
O sistema opioide contribui para o efeito do tipo antidepressivo do disseleneto de m-trifluormetil-difenila em camundongos |
title_full |
O sistema opioide contribui para o efeito do tipo antidepressivo do disseleneto de m-trifluormetil-difenila em camundongos |
title_fullStr |
O sistema opioide contribui para o efeito do tipo antidepressivo do disseleneto de m-trifluormetil-difenila em camundongos |
title_full_unstemmed |
O sistema opioide contribui para o efeito do tipo antidepressivo do disseleneto de m-trifluormetil-difenila em camundongos |
title_sort |
O sistema opioide contribui para o efeito do tipo antidepressivo do disseleneto de m-trifluormetil-difenila em camundongos |
author |
Rosa, Suzan Gonçalves |
author_facet |
Rosa, Suzan Gonçalves |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Nogueira, Cristina Wayne |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/2877042401245169 |
dc.contributor.referee1.fl_str_mv |
Torres, Iraci Lucena da Silva |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/3765572633415830 |
dc.contributor.referee2.fl_str_mv |
Franco, Jeferson Luis |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/1680065573338339 |
dc.contributor.referee3.fl_str_mv |
Prigol, Marina |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/6724052141066150 |
dc.contributor.referee4.fl_str_mv |
Oliveira, Mauro Schneider |
dc.contributor.referee4Lattes.fl_str_mv |
http://lattes.cnpq.br/7132934163734175 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/4191126676996771 |
dc.contributor.author.fl_str_mv |
Rosa, Suzan Gonçalves |
contributor_str_mv |
Nogueira, Cristina Wayne Torres, Iraci Lucena da Silva Franco, Jeferson Luis Prigol, Marina Oliveira, Mauro Schneider |
dc.subject.por.fl_str_mv |
Depressão Selênio Sistema opioide Estresse |
topic |
Depressão Selênio Sistema opioide Estresse Depression Selenium Opioid system Stress CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Depression Selenium Opioid system Stress |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Depression is a mental disorder with complex pathophysiology and characterized by multiple symptoms, which makes it difficult to treat this disease. In the last decades, the opioid system has become the focus of depression researches, given that this system has an important regulatory effect on mood. However, the opioids use in the clinic is limited by the development of tolerance and dependence after repeated administration. The organoselenium compound m-trifluoromethyl-diphenyl diselenide (m-CF3-PhSe)2 elicits antidepressant-like effect in animal models through different action targets, including the opioid system. Thus, the main objective of this thesis was to evaluate the opioid system contribution to the pharmacological effect of the organic compound of selenium (m-CF3-PhSe)2 in models of depression in swiss male mice. The results of article 1 demonstrated the (m-CF3-PhSe)2 antidepressant-like effect on the forced swimming test (FST) and the contribution of each opioid receptor to this effect through the use of selective antagonists of these receptors, suggesting that μ and δ receptors activation and κ-receptor blockade are involved in the antidepressant-like action of the compound. In addition, article 1 revealed the antidepressant-like effect of acute or repeated administration of (m-CF3-PhSe)2 on the FST and the modified tail suspension test (TST). In the modified TST, the involvement of the opioid system in the antidepressant-like action of the compound was demonstrated by the increase of behaviors characteristic of opioid system modulation. The article 1 also demonstrated that repeated administration of (m-CF3-PhSe)2 neither induce tolerance in the FST nor physical signs of naloxone-induced withdrawal and did not alter systemic toxicity parameters. Based on these results, it was investigated the molecular mechanisms by which the opioid system contributes to the antidepressant-like effect of (m- CF3-PhSe)2. For this, stress-induced depression models were carried out, given that the opioid system is involved in the different responses to stress. The article 2 revealed that one or repeated forced swimming stress (FSS) exposures induced depressant-like behavior and affected the prefrontal cortical opioid receptor levels of mice. In this study, (m-CF3-PhSe)2 was effective against depressant-like symptoms induced by repeated FSS in the FST, the TST and the splash test through of μ and κ receptor levels regulation. Therefore, the (m-CF3- PhSe)2 effect was investigated in a more severe and prolonged stress model in the article 3. In this study, social defeat stress (SDS) induced social aversion and altered the levels of the three opioid receptors types in the prefrontal cortex of susceptible mice. (m-CF3-PhSe)2 was effective against these changes, promoting resilience to SDS and increasing the natural sociability among mice. Together, the results of this thesis contributes to the understanding of the opioid mechanisms involved in the antidepressant-like effect of (m-CF3-PhSe)2 and indicates that this compound may be an therapeutic alternative for the treatment of depression. |
publishDate |
2018 |
dc.date.accessioned.fl_str_mv |
2018-11-26T13:06:47Z |
dc.date.available.fl_str_mv |
2018-11-26T13:06:47Z |
dc.date.issued.fl_str_mv |
2018-07-20 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/14934 |
url |
http://repositorio.ufsm.br/handle/1/14934 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
200800000002 |
dc.relation.confidence.fl_str_mv |
600 |
dc.relation.authority.fl_str_mv |
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dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Bioquímica |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional Manancial UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Repositório Institucional Manancial UFSM |
collection |
Repositório Institucional Manancial UFSM |
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http://repositorio.ufsm.br/bitstream/1/14934/1/TES_PPGCBBT_2018_ROSA_SUZAN.pdf http://repositorio.ufsm.br/bitstream/1/14934/2/license_rdf http://repositorio.ufsm.br/bitstream/1/14934/3/license.txt http://repositorio.ufsm.br/bitstream/1/14934/4/TES_PPGCBBT_2018_ROSA_SUZAN.pdf.txt http://repositorio.ufsm.br/bitstream/1/14934/5/TES_PPGCBBT_2018_ROSA_SUZAN.pdf.jpg |
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bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional Manancial UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
ouvidoria@ufsm.br |
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1808854723447488512 |