Avaliação do modelo de transtorno de estresse póstraumático (TEPT) e camundongos machos : efeitos do midazolam, sertralina e ausência de efeito da imipramina

Detalhes bibliográficos
Ano de defesa: 2008
Autor(a) principal: Costa, Fernando de Souza Melo
Orientador(a): Souza, Azair Liane Matos do Canto de lattes
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal de São Carlos
Programa de Pós-Graduação: Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas - PIPGCF
Departamento: Não Informado pela instituição
País: BR
Palavras-chave em Português:
Palavras-chave em Inglês:
Área do conhecimento CNPq:
Link de acesso: https://repositorio.ufscar.br/handle/20.500.14289/1299
Resumo: The post-traumatic stress disorder (PTSD) affects a portion of subjects exposed to a traumatic event. This disorder leads to long-term alterations in the hypothalamus-pituitaryadrenal (HPA) axis, autonomic and cognitive function. The aim of our study was to evaluate whether the animal model of PTSD proposed for rats could be used in mice and, to evaluate the effect of benzodiazepine, tricycle antidepressant and selective serotonin reuptake inhibitor drugs in the PTSD model. For this we realized the following experiments: Experiment 1- The test consisted of exposure the male mice to inescapable electric footshock (0.3 mA) in the black side (BS) of the black-white box (BW). In the 7th, 14th and 21th day, mice were reexposed to the traumatic reminder on the white side (WS) or BS for 2 min, without footshock. In the 29th day, the animals were submitted to elevated plus-maze (EPM) for record the anxiety indexes [percentage of open arm entries (%OA) and percentage of open arm time (%OT) and as well as general locomotor activity, closed arm entries (CE)]. On day 34 the same animals were submitted to BW test for record the latency to escape (LE) from WS and time spent on WS of the BW box. Experiment 2 the same procedure of experiment 1 was performed, except that the animals were re-exposed at 7th, 14th e 21th days to reminder situation only in WS of BW box for 2 min, without footshock. On day 29th, the animals were exposed to EPM, 30 min after receiving treatment with midazolam. In 34th day the same animals after receiving treatment with midazolam were submitted to BW box test. Experiment 3, 4 and 5 - the same procedure was adopted from experiment 2, except that in 29th day, the animals were not submitted to EPM test and on 34th day 30 minutes after treatment with midazolam, imipramine and sertraline were submitted to BW box. Two-way ANOVA (stimulus x place remainder or treatment) followed by Duncan test showed that PTSD model increased anxiety in mice (P<0.05). The re-exposure in BS promoted anxiogenic-like effect extinction of the model. The midazolam treatment (1.0 and 2.0 mg/kg, i.p.) produced anxiolytic-like effect in maze-mice (P < 0.05) and the 0.5 mg/kg decreased latency to escape of WS (P < 0.05) of BW box and increased the exploratory activity, suggesting involvement of this GABA-benzodiazepine agonist on this PTSD modulation. The EPM test does not interfere in the evaluation of the BW test. It is important to note that no other behaviors were significantly altered by imipramine per se (P < 0.05). The sertraline (5.0 mg/kg), selective serotonin reuptake inhibitor, produced anxiolytic-like effect in the BW test (P < 0.05) and increase exploration activity. These results suggest that the employed PTSD model to study neurobiological disturbances associated with this disorder.
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spelling Costa, Fernando de Souza MeloSouza, Azair Liane Matos do Canto dehttp://lattes.cnpq.br/2352004564367849http://lattes.cnpq.br/2982118089291826995ef310-68f4-46c9-91ad-58842cbba77c2016-06-02T19:22:49Z2008-08-222016-06-02T19:22:49Z2008-05-21COSTA, Fernando de Souza Melo. Avaliação do modelo de transtorno de estresse póstraumático (TEPT) e camundongos machos : efeitos do midazolam, sertralina e ausência de efeito da imipramina. 2008. 84 f. Dissertação (Mestrado em Ciências Biológicas) - Universidade Federal de São Carlos, São Carlos, 2008.https://repositorio.ufscar.br/handle/20.500.14289/1299The post-traumatic stress disorder (PTSD) affects a portion of subjects exposed to a traumatic event. This disorder leads to long-term alterations in the hypothalamus-pituitaryadrenal (HPA) axis, autonomic and cognitive function. The aim of our study was to evaluate whether the animal model of PTSD proposed for rats could be used in mice and, to evaluate the effect of benzodiazepine, tricycle antidepressant and selective serotonin reuptake inhibitor drugs in the PTSD model. For this we realized the following experiments: Experiment 1- The test consisted of exposure the male mice to inescapable electric footshock (0.3 mA) in the black side (BS) of the black-white box (BW). In the 7th, 14th and 21th day, mice were reexposed to the traumatic reminder on the white side (WS) or BS for 2 min, without footshock. In the 29th day, the animals were submitted to elevated plus-maze (EPM) for record the anxiety indexes [percentage of open arm entries (%OA) and percentage of open arm time (%OT) and as well as general locomotor activity, closed arm entries (CE)]. On day 34 the same animals were submitted to BW test for record the latency to escape (LE) from WS and time spent on WS of the BW box. Experiment 2 the same procedure of experiment 1 was performed, except that the animals were re-exposed at 7th, 14th e 21th days to reminder situation only in WS of BW box for 2 min, without footshock. On day 29th, the animals were exposed to EPM, 30 min after receiving treatment with midazolam. In 34th day the same animals after receiving treatment with midazolam were submitted to BW box test. Experiment 3, 4 and 5 - the same procedure was adopted from experiment 2, except that in 29th day, the animals were not submitted to EPM test and on 34th day 30 minutes after treatment with midazolam, imipramine and sertraline were submitted to BW box. Two-way ANOVA (stimulus x place remainder or treatment) followed by Duncan test showed that PTSD model increased anxiety in mice (P<0.05). The re-exposure in BS promoted anxiogenic-like effect extinction of the model. The midazolam treatment (1.0 and 2.0 mg/kg, i.p.) produced anxiolytic-like effect in maze-mice (P < 0.05) and the 0.5 mg/kg decreased latency to escape of WS (P < 0.05) of BW box and increased the exploratory activity, suggesting involvement of this GABA-benzodiazepine agonist on this PTSD modulation. The EPM test does not interfere in the evaluation of the BW test. It is important to note that no other behaviors were significantly altered by imipramine per se (P < 0.05). The sertraline (5.0 mg/kg), selective serotonin reuptake inhibitor, produced anxiolytic-like effect in the BW test (P < 0.05) and increase exploration activity. These results suggest that the employed PTSD model to study neurobiological disturbances associated with this disorder.O Transtorno de Estresse Pós-Traumático (TEPT) afeta uma parcela de indivíduos que são expostos a um evento traumático. Este distúrbio induz em longo prazo alterações no eixo HPA, autonômicas e cognitivas. O objetivo deste estudo foi avaliar se o modelo animal de TEPT proposto para ratos poderia ser utilizado em camundongos e investigar o efeito dos fármacos benzodiazepínico, antidepressivo tricíclico e inibidor seletivo da recaptação de serotonina, no modelo de TEPT. Para isso realizamos os seguintes experimentos: Experimento 1- O teste consistiu em submeter camundongos machos, Suíço-albino ao choque inescapável (0,3mA) nas patas no lado escuro (LE) da caixa claro-escuro (CE). No 7º, 14º e 21º dia os camundongos foram reexpostos a situação de lembrança no lado claro (LC) ou LE da caixa por 2 min, sem choque. No 29º dia os animais foram expostos ao labirinto em cruz elevado (LCE), para o registro dos índices de ansiedade [porcentagem de entradas (%EBA) e de tempo gasto nos braços abertos (%TBA) e atividade locomotora, entrada nos braços fechados (EBF)]. No 34º dia os mesmos animais foram submetidos ao teste CE para o registro da latência de fuga (LF) e do tempo gasto no LC da caixa CE. Experimento 2 o mesmo procedimento do experimento 1 foi adotado, exceto que os animais foram reexpostos no 7º, 14º e 21º dia a situação de lembrança apenas no LC da caixa por 2 min, sem choque. No 29º dia os animais, 30 min após receberem tratamento com midazolam, foram expostos ao labirinto em cruz elevado (LCE). No 34º dia os mesmos animais após receberem o mesmo tratamento farmacológico, foram submetidos ao teste CE. Experimento 3, 4 e 5 o mesmo procedimento do experimento 2 foi adotado, exceto que no 29º dia os animais não foram submetidos ao LCE e no 34º dia, 30 min após receberem tratamento com midazolam, imipramina e sertralina foram submetidos ao teste CE. A ANOVA de duas vias (estímulo x local da SL ou tratamento) seguido do teste de Duncan mostrou que o modelo de TEPT produziu aumento da ansiedade nos camundongos (P < 0,05). As reexposições no LE promoveram extinção do efeito ansiogênico do modelo. O tratamento com midazolam (1,0 e 2,0 mg/kg) produziu efeito ansiolítico no LCE (P < 0,05), e a dose de 0,5 mg/kg reduziu a latência de fuga do ambiente claro (P < 0,05) no teste CE e aumentou a atividade exploratória, sugerindo o envolvimento deste agonista GABA-benzodiazepínico na modulação do TEPT. O LCE não interferiu na avaliação do teste CE. A imipramina não apresentou efeito sobre os camundongos (P > 0,05), ou seja, ausência de efeito deste antidepressivo tricíclico nos sintomas do TEPT. A sertralina (5,0 mg/kg) produziu efeito ansiolítico no teste CE (P < 0,05) e aumento na atividade exploratória, mostrando o envolvimento deste inibidor seletivo da recaptação de serotonina na modulação do modelo. Estes resultados sugerem que o modelo de TEPT utilizado poderá ser empregado para o estudo das alterações neurobiológicas envolvidas neste distúrbio.Financiadora de Estudos e Projetosapplication/pdfporUniversidade Federal de São CarlosPrograma Interinstitucional de Pós-Graduação em Ciências Fisiológicas - PIPGCFUFSCarBRPsicofarmacologiaAnsiedadeCamundongoLabirinto em cruz elevadoTranstorno do stress póstraumáticoClaro-escuroPost-traumatic stress disorderAnxietyMidazolamImipramineSertralineElevated plus-mazeBlack white testCIENCIAS BIOLOGICAS::FISIOLOGIAAvaliação do modelo de transtorno de estresse póstraumático (TEPT) e camundongos machos : efeitos do midazolam, sertralina e ausência de efeito da imipraminainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis-1-1ec59bf11-8f1b-4d55-a0dd-35037d3bb124info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARTEXT1958.pdf.txt1958.pdf.txtExtracted texttext/plain101784https://repositorio.ufscar.br/bitstreams/adb645e9-8413-4558-a511-70eaef1272f2/download28fb0563b83cdf5706d7c5f34c839427MD53falseAnonymousREADORIGINAL1958.pdfapplication/pdf10581288https://repositorio.ufscar.br/bitstreams/95a2c6f5-24e8-4fea-9554-af7c86b5c442/download1dc2b5264737849b6a8842144f1ad052MD51trueAnonymousREADTHUMBNAIL1958.pdf.jpg1958.pdf.jpgIM Thumbnailimage/jpeg5800https://repositorio.ufscar.br/bitstreams/8f2f2adf-6aa5-4684-a443-de044a793d9f/download40e5cc9e41efecbe4aede113d53a1e6fMD52falseAnonymousREAD20.500.14289/12992025-02-05 15:07:04.046open.accessoai:repositorio.ufscar.br:20.500.14289/1299https://repositorio.ufscar.brRepositório InstitucionalPUBhttps://repositorio.ufscar.br/oai/requestrepositorio.sibi@ufscar.bropendoar:43222025-02-05T18:07:04Repositório Institucional da UFSCAR - Universidade Federal de São Carlos (UFSCAR)false
dc.title.por.fl_str_mv Avaliação do modelo de transtorno de estresse póstraumático (TEPT) e camundongos machos : efeitos do midazolam, sertralina e ausência de efeito da imipramina
title Avaliação do modelo de transtorno de estresse póstraumático (TEPT) e camundongos machos : efeitos do midazolam, sertralina e ausência de efeito da imipramina
spellingShingle Avaliação do modelo de transtorno de estresse póstraumático (TEPT) e camundongos machos : efeitos do midazolam, sertralina e ausência de efeito da imipramina
Costa, Fernando de Souza Melo
Psicofarmacologia
Ansiedade
Camundongo
Labirinto em cruz elevado
Transtorno do stress póstraumático
Claro-escuro
Post-traumatic stress disorder
Anxiety
Midazolam
Imipramine
Sertraline
Elevated plus-maze
Black white test
CIENCIAS BIOLOGICAS::FISIOLOGIA
title_short Avaliação do modelo de transtorno de estresse póstraumático (TEPT) e camundongos machos : efeitos do midazolam, sertralina e ausência de efeito da imipramina
title_full Avaliação do modelo de transtorno de estresse póstraumático (TEPT) e camundongos machos : efeitos do midazolam, sertralina e ausência de efeito da imipramina
title_fullStr Avaliação do modelo de transtorno de estresse póstraumático (TEPT) e camundongos machos : efeitos do midazolam, sertralina e ausência de efeito da imipramina
title_full_unstemmed Avaliação do modelo de transtorno de estresse póstraumático (TEPT) e camundongos machos : efeitos do midazolam, sertralina e ausência de efeito da imipramina
title_sort Avaliação do modelo de transtorno de estresse póstraumático (TEPT) e camundongos machos : efeitos do midazolam, sertralina e ausência de efeito da imipramina
author Costa, Fernando de Souza Melo
author_facet Costa, Fernando de Souza Melo
author_role author
dc.contributor.authorlattes.por.fl_str_mv http://lattes.cnpq.br/2982118089291826
dc.contributor.author.fl_str_mv Costa, Fernando de Souza Melo
dc.contributor.advisor1.fl_str_mv Souza, Azair Liane Matos do Canto de
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/2352004564367849
dc.contributor.authorID.fl_str_mv 995ef310-68f4-46c9-91ad-58842cbba77c
contributor_str_mv Souza, Azair Liane Matos do Canto de
dc.subject.por.fl_str_mv Psicofarmacologia
Ansiedade
Camundongo
Labirinto em cruz elevado
Transtorno do stress póstraumático
Claro-escuro
topic Psicofarmacologia
Ansiedade
Camundongo
Labirinto em cruz elevado
Transtorno do stress póstraumático
Claro-escuro
Post-traumatic stress disorder
Anxiety
Midazolam
Imipramine
Sertraline
Elevated plus-maze
Black white test
CIENCIAS BIOLOGICAS::FISIOLOGIA
dc.subject.eng.fl_str_mv Post-traumatic stress disorder
Anxiety
Midazolam
Imipramine
Sertraline
Elevated plus-maze
Black white test
dc.subject.cnpq.fl_str_mv CIENCIAS BIOLOGICAS::FISIOLOGIA
description The post-traumatic stress disorder (PTSD) affects a portion of subjects exposed to a traumatic event. This disorder leads to long-term alterations in the hypothalamus-pituitaryadrenal (HPA) axis, autonomic and cognitive function. The aim of our study was to evaluate whether the animal model of PTSD proposed for rats could be used in mice and, to evaluate the effect of benzodiazepine, tricycle antidepressant and selective serotonin reuptake inhibitor drugs in the PTSD model. For this we realized the following experiments: Experiment 1- The test consisted of exposure the male mice to inescapable electric footshock (0.3 mA) in the black side (BS) of the black-white box (BW). In the 7th, 14th and 21th day, mice were reexposed to the traumatic reminder on the white side (WS) or BS for 2 min, without footshock. In the 29th day, the animals were submitted to elevated plus-maze (EPM) for record the anxiety indexes [percentage of open arm entries (%OA) and percentage of open arm time (%OT) and as well as general locomotor activity, closed arm entries (CE)]. On day 34 the same animals were submitted to BW test for record the latency to escape (LE) from WS and time spent on WS of the BW box. Experiment 2 the same procedure of experiment 1 was performed, except that the animals were re-exposed at 7th, 14th e 21th days to reminder situation only in WS of BW box for 2 min, without footshock. On day 29th, the animals were exposed to EPM, 30 min after receiving treatment with midazolam. In 34th day the same animals after receiving treatment with midazolam were submitted to BW box test. Experiment 3, 4 and 5 - the same procedure was adopted from experiment 2, except that in 29th day, the animals were not submitted to EPM test and on 34th day 30 minutes after treatment with midazolam, imipramine and sertraline were submitted to BW box. Two-way ANOVA (stimulus x place remainder or treatment) followed by Duncan test showed that PTSD model increased anxiety in mice (P<0.05). The re-exposure in BS promoted anxiogenic-like effect extinction of the model. The midazolam treatment (1.0 and 2.0 mg/kg, i.p.) produced anxiolytic-like effect in maze-mice (P < 0.05) and the 0.5 mg/kg decreased latency to escape of WS (P < 0.05) of BW box and increased the exploratory activity, suggesting involvement of this GABA-benzodiazepine agonist on this PTSD modulation. The EPM test does not interfere in the evaluation of the BW test. It is important to note that no other behaviors were significantly altered by imipramine per se (P < 0.05). The sertraline (5.0 mg/kg), selective serotonin reuptake inhibitor, produced anxiolytic-like effect in the BW test (P < 0.05) and increase exploration activity. These results suggest that the employed PTSD model to study neurobiological disturbances associated with this disorder.
publishDate 2008
dc.date.available.fl_str_mv 2008-08-22
2016-06-02T19:22:49Z
dc.date.issued.fl_str_mv 2008-05-21
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dc.identifier.citation.fl_str_mv COSTA, Fernando de Souza Melo. Avaliação do modelo de transtorno de estresse póstraumático (TEPT) e camundongos machos : efeitos do midazolam, sertralina e ausência de efeito da imipramina. 2008. 84 f. Dissertação (Mestrado em Ciências Biológicas) - Universidade Federal de São Carlos, São Carlos, 2008.
dc.identifier.uri.fl_str_mv https://repositorio.ufscar.br/handle/20.500.14289/1299
identifier_str_mv COSTA, Fernando de Souza Melo. Avaliação do modelo de transtorno de estresse póstraumático (TEPT) e camundongos machos : efeitos do midazolam, sertralina e ausência de efeito da imipramina. 2008. 84 f. Dissertação (Mestrado em Ciências Biológicas) - Universidade Federal de São Carlos, São Carlos, 2008.
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