Desenvolvimento de um modelo experimental de transtorno bipolar bifásico em ratos

Detalhes bibliográficos
Ano de defesa: 2019
Autor(a) principal: Barroso, Poliana Noronha
Orientador(a): Aragão, Gislei Frota
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: http://www.repositorio.ufc.br/handle/riufc/74045
Resumo: Bipolar disorder (BD) is a serious and disabling psychiatric condition that affects 2% of the world's population. Clinically, it is characterized by a cyclic variation of mood phases, between mania (or euphoria) and depression. Due to its clinical complexity, the development of an animal model that effectively reproduces BD remains a challenge for researchers in this field. In scientific literature, the use of animal models to mimic BD has focused on separate phases of the disorder, and few studies have validated strategies that include both manic and depressive phases in one experimental trajectory. The development of an animal model involves the validation of three criteria: a) face validity, which refers to how adequately the model induces the signs and symptoms of the modeled disease; b) the construct validity, which analyzes the ability of a model to reproduce the etiopathological process and the pathophysiological mechanisms of the disease and its biological alterations; and c) the predictive (pharmacological) validity, in which we assess the model's response to therapeutic approaches to the disease, if it can be reversed or attenuated with treatment, and if we can predict the effects of the intervention in human subjects. In this study, we developed a model of BD induced by repeated administration of amphetamine in rats. For this, male Wistar rats were treated with amphetamine in two different protocols, to induce manic and depressive symptoms. In the manic phenotype, the animals received 7 days of amphetamine treatment (2.0 mg/kg). On the seventh day, the rats underwent behavioral testing and were sacrificed for removal of brain areas. For the depressive phenotype, the animals received 7 days of amphetamine treatment (2.0 mg/kg), which was suspended from the 8th to the 21st day. After this period, the rats were equally evaluated and sacrificed. Additionally, a group of lithium-treated animals was included in each protocol, to assess the reversal potential of model-induced changes. The results showed that the Phase Mania protocol promoted manic-type behavior in animals. In the Phase Depression protocol, the Sucrose Preference test promoted depressive-type behavior, which is highly relevant in the assessment of depression. Further research will be needed to consolidate this two-phase model in the study of Bipolar Disorder.
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spelling Barroso, Poliana NoronhaMoraes, Maria Elisabete Amaral de MoraesAragão, Gislei Frota2023-08-22T10:39:19Z2023-08-22T10:39:19Z2019BARROSO, Poliana Noronha. Desenvolvimento de um modelo experimental de transtorno bipolar bifásico em ratos. 2019. 45 f. Dissertação (Mestrado Profissional em Farmacologia Clínica) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2019. Disponível em: http://www.repositorio.ufc.br/handle/riufc/74045. Acesso em: 22 ago. 2023.http://www.repositorio.ufc.br/handle/riufc/74045Bipolar disorder (BD) is a serious and disabling psychiatric condition that affects 2% of the world's population. Clinically, it is characterized by a cyclic variation of mood phases, between mania (or euphoria) and depression. Due to its clinical complexity, the development of an animal model that effectively reproduces BD remains a challenge for researchers in this field. In scientific literature, the use of animal models to mimic BD has focused on separate phases of the disorder, and few studies have validated strategies that include both manic and depressive phases in one experimental trajectory. The development of an animal model involves the validation of three criteria: a) face validity, which refers to how adequately the model induces the signs and symptoms of the modeled disease; b) the construct validity, which analyzes the ability of a model to reproduce the etiopathological process and the pathophysiological mechanisms of the disease and its biological alterations; and c) the predictive (pharmacological) validity, in which we assess the model's response to therapeutic approaches to the disease, if it can be reversed or attenuated with treatment, and if we can predict the effects of the intervention in human subjects. In this study, we developed a model of BD induced by repeated administration of amphetamine in rats. For this, male Wistar rats were treated with amphetamine in two different protocols, to induce manic and depressive symptoms. In the manic phenotype, the animals received 7 days of amphetamine treatment (2.0 mg/kg). On the seventh day, the rats underwent behavioral testing and were sacrificed for removal of brain areas. For the depressive phenotype, the animals received 7 days of amphetamine treatment (2.0 mg/kg), which was suspended from the 8th to the 21st day. After this period, the rats were equally evaluated and sacrificed. Additionally, a group of lithium-treated animals was included in each protocol, to assess the reversal potential of model-induced changes. The results showed that the Phase Mania protocol promoted manic-type behavior in animals. In the Phase Depression protocol, the Sucrose Preference test promoted depressive-type behavior, which is highly relevant in the assessment of depression. Further research will be needed to consolidate this two-phase model in the study of Bipolar Disorder.O transtorno bipolar (TB) é uma condição psiquiátrica séria e incapacitante, que atinge 2% da população mundial. Clinicamente, caracteriza-se por uma variação cíclica de fases do humor, entre a mania (ou euforia) e a depressão. Em decorrência de sua complexidade clínica, o desenvolvimento de um modelo animal que reproduza eficazmente o TB permanece um desafio para os pesquisadores da área. Na literatura científica, o uso de modelos animais para mimetizar o TB têm focado nas fases separadas do transtorno, e poucos estudos têm validado estratégias que incluam as fases de euforia e depressão em uma só trajetória experimental. O desenvolvimento de um modelo animal envolve a validação de três critérios: a) a validade aparente (de face), que se refere a quão adequadamente o modelo induz os sinais e sintomas da doença modelada; b) a validade de constructo (etiológica), que analisa a capacidade de um modelo reproduzir o processo etiopatológico e os mecanismos fisiopatológicos da doença e suas alterações biológicas; e c) a validade preditiva (farmacológica), na qual se avalia a resposta do modelo a abordagens terapêuticas para a doença em questão, se esta pode ser revertida ou atenuada por um tratamento, e se é possível predizer os efeitos da intervenção em seres humanos. O objetivo do presente estudo foi desenvolver um modelo de TB induzido pela administração repetida de anfetamina em ratos. Para tanto, ratos Wistar machos receberam anfetamina em dois protocolos distintos, para induzir sintomas tipo-maníaco e tipo-depressivo. No fenótipo maníaco, os animais receberam 7 dias de tratamento com anfetamina (2,0 mg/kg). No sétimo dia, os ratos foram submetidos a testes comportamentais. Para o fenótipo depressivo, os animais receberam anfetamina (2,0 mg/kg) por 7 dias, a qual foi suspensa do 8º ao 21º dia. Findo este período, os ratos foram igualmente submetidos aos testes de comportamento. Adicionalmente, um grupo de animais tratados com lítio foi incluído em cada protocolo, a fim de avaliar o potencial de reversão das alterações induzidas pelo modelo. Os resultados mostraram que o protocolo da Fase Mania promoveu comportamento tipo-maníaco nos animais. No protocolo Fase Depressão, o teste da Preferência por Sacarose evidenciou comportamento tipo-depressivo, o qual tem alta relevância na avaliação da depressão. O desenvolvimento de pesquisas adicionais será necessário para consolidar este modelo de duas fases no estudo de Transtorno Bipolar.Transtorno BipolarManiaDepressãoAnfetaminaDesenvolvimento de um modelo experimental de transtorno bipolar bifásico em ratosinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccessORIGINAL2023_dis_pnbarroso.pdf2023_dis_pnbarroso.pdfapplication/pdf669385http://repositorio.ufc.br/bitstream/riufc/74045/1/2023_dis_pnbarroso.pdf72950036e456af81be8d6b01e8fa600bMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/74045/3/license.txt8a4605be74aa9ea9d79846c1fba20a33MD53riufc/740452023-08-22 07:42:27.265oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2023-08-22T10:42:27Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Desenvolvimento de um modelo experimental de transtorno bipolar bifásico em ratos
title Desenvolvimento de um modelo experimental de transtorno bipolar bifásico em ratos
spellingShingle Desenvolvimento de um modelo experimental de transtorno bipolar bifásico em ratos
Barroso, Poliana Noronha
Transtorno Bipolar
Mania
Depressão
Anfetamina
title_short Desenvolvimento de um modelo experimental de transtorno bipolar bifásico em ratos
title_full Desenvolvimento de um modelo experimental de transtorno bipolar bifásico em ratos
title_fullStr Desenvolvimento de um modelo experimental de transtorno bipolar bifásico em ratos
title_full_unstemmed Desenvolvimento de um modelo experimental de transtorno bipolar bifásico em ratos
title_sort Desenvolvimento de um modelo experimental de transtorno bipolar bifásico em ratos
author Barroso, Poliana Noronha
author_facet Barroso, Poliana Noronha
author_role author
dc.contributor.co-advisor.none.fl_str_mv Moraes, Maria Elisabete Amaral de Moraes
dc.contributor.author.fl_str_mv Barroso, Poliana Noronha
dc.contributor.advisor1.fl_str_mv Aragão, Gislei Frota
contributor_str_mv Aragão, Gislei Frota
dc.subject.por.fl_str_mv Transtorno Bipolar
Mania
Depressão
Anfetamina
topic Transtorno Bipolar
Mania
Depressão
Anfetamina
description Bipolar disorder (BD) is a serious and disabling psychiatric condition that affects 2% of the world's population. Clinically, it is characterized by a cyclic variation of mood phases, between mania (or euphoria) and depression. Due to its clinical complexity, the development of an animal model that effectively reproduces BD remains a challenge for researchers in this field. In scientific literature, the use of animal models to mimic BD has focused on separate phases of the disorder, and few studies have validated strategies that include both manic and depressive phases in one experimental trajectory. The development of an animal model involves the validation of three criteria: a) face validity, which refers to how adequately the model induces the signs and symptoms of the modeled disease; b) the construct validity, which analyzes the ability of a model to reproduce the etiopathological process and the pathophysiological mechanisms of the disease and its biological alterations; and c) the predictive (pharmacological) validity, in which we assess the model's response to therapeutic approaches to the disease, if it can be reversed or attenuated with treatment, and if we can predict the effects of the intervention in human subjects. In this study, we developed a model of BD induced by repeated administration of amphetamine in rats. For this, male Wistar rats were treated with amphetamine in two different protocols, to induce manic and depressive symptoms. In the manic phenotype, the animals received 7 days of amphetamine treatment (2.0 mg/kg). On the seventh day, the rats underwent behavioral testing and were sacrificed for removal of brain areas. For the depressive phenotype, the animals received 7 days of amphetamine treatment (2.0 mg/kg), which was suspended from the 8th to the 21st day. After this period, the rats were equally evaluated and sacrificed. Additionally, a group of lithium-treated animals was included in each protocol, to assess the reversal potential of model-induced changes. The results showed that the Phase Mania protocol promoted manic-type behavior in animals. In the Phase Depression protocol, the Sucrose Preference test promoted depressive-type behavior, which is highly relevant in the assessment of depression. Further research will be needed to consolidate this two-phase model in the study of Bipolar Disorder.
publishDate 2019
dc.date.issued.fl_str_mv 2019
dc.date.accessioned.fl_str_mv 2023-08-22T10:39:19Z
dc.date.available.fl_str_mv 2023-08-22T10:39:19Z
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dc.identifier.citation.fl_str_mv BARROSO, Poliana Noronha. Desenvolvimento de um modelo experimental de transtorno bipolar bifásico em ratos. 2019. 45 f. Dissertação (Mestrado Profissional em Farmacologia Clínica) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2019. Disponível em: http://www.repositorio.ufc.br/handle/riufc/74045. Acesso em: 22 ago. 2023.
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/74045
identifier_str_mv BARROSO, Poliana Noronha. Desenvolvimento de um modelo experimental de transtorno bipolar bifásico em ratos. 2019. 45 f. Dissertação (Mestrado Profissional em Farmacologia Clínica) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2019. Disponível em: http://www.repositorio.ufc.br/handle/riufc/74045. Acesso em: 22 ago. 2023.
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