O tratamento crônico com fluoxetina reverte os efeitos nociceptivo e antinociceptivo induzidos pela ativação dos receptores 5-HT1A e 5-HT2C da amídala de camundongos confinados aos braços do labirinto em cruz elevado

Detalhes bibliográficos
Autor(a) principal: Furuya-da-Cunha, Elke Mayumi
Data de Publicação: 2019
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da UFSCAR
Texto Completo: https://repositorio.ufscar.br/handle/ufscar/11752
Resumo: Several studies indicate that anxiety and depression may be accompanied by symptoms of severe pain with no precise location or apparent lesions. Several evidences demonstrate that some antidepressive drugs used in the treatment of these emotional disorders are also effective in the relief of pain. The interaction between emotional and sensorial responses is of high relevance for the survival of the species. Several studies have shown that exposure to threatening situations results in behavioral and physiological defense reactions that be accompanied by inhibition of pain. The amygdala, a subcortical nucleus complex, has been shown to be involved in the mechanism of fear-induced antinociception. And it being a complex of interface between the sensorial and emotional stimuli. Evidences have shown that stimulation of this structure can induce fear or anxiety reactions, accompanied by analgesia, thus suggesting its participation in the defense system and nociception modulation.The elevated plus maze (EPM) is an apparatus used to assess rodent anxiety and it is sensitive to anxiolytic and anxiogenic effect of drugs. In this sense, EPM is used to study the neurobiology of antinociception induced by the aversive potential of the open arms experiment. Thus, considering evidences of the antiaversive role of serotonin in the amygdala, observed with chronic treatment with serotonin reuptake inhibitors, this study aimed to evaluate the role of amygdala 5-HT1A and 5-HT2C serotonin receptor subtypes on nociception and antinociception effects of mice exposed to the EPM in this context. For this, 5-HT1A (8-OH-DPAT) and 5-HT2C (MK-212) receptor agonists were microinjected intra-amygdala associated with chronic systemic treatment of fluoxetine in mice. The animals were confined in the enclosed or open arm of the EPM and the number of abdominal writings after the intraperitoneal (i.p.) injection of acetic acid solution was counted. Intra-amygdala treatment with 8-OH-DPAT produced an increase in the number of writhes in both mice that were confined in the open arm and those that were confined in the enclosed arm. However, treatment fluoxetine + 8-OH-DPAT blocked the effect of intra-amygdala injection only for the mice confined in the open arm. Intra-amygdala treatment with MK-212 produced a decrease in the number of writhes only in mice that were confined to the open arm, and the fluoxetine + MK-212 treatment impaired this effect. These results suggest that chronic treatment with fluoxetine reversed the effects produced by the activation of the 5-HT1A and 5-HT2C receptors in the amygdala of mice confined to the EPM.
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spelling Furuya-da-Cunha, Elke MayumiSouza, Azair Liane Matos do Canto dehttp://lattes.cnpq.br/2352004564367849http://lattes.cnpq.br/9582420020561046c338a839-5bcb-4d08-bd3c-e45ce7af230b2019-08-20T14:57:09Z2019-08-20T14:57:09Z2019-05-31FURUYA-DA-CUNHA, Elke Mayumi. O tratamento crônico com fluoxetina reverte os efeitos nociceptivo e antinociceptivo induzidos pela ativação dos receptores 5-HT1A e 5-HT2C da amídala de camundongos confinados aos braços do labirinto em cruz elevado. 2019. Tese (Doutorado em Ciências Fisiológicas) – Universidade Federal de São Carlos, São Carlos, 2019. Disponível em: https://repositorio.ufscar.br/handle/ufscar/11752.https://repositorio.ufscar.br/handle/ufscar/11752Several studies indicate that anxiety and depression may be accompanied by symptoms of severe pain with no precise location or apparent lesions. Several evidences demonstrate that some antidepressive drugs used in the treatment of these emotional disorders are also effective in the relief of pain. The interaction between emotional and sensorial responses is of high relevance for the survival of the species. Several studies have shown that exposure to threatening situations results in behavioral and physiological defense reactions that be accompanied by inhibition of pain. The amygdala, a subcortical nucleus complex, has been shown to be involved in the mechanism of fear-induced antinociception. And it being a complex of interface between the sensorial and emotional stimuli. Evidences have shown that stimulation of this structure can induce fear or anxiety reactions, accompanied by analgesia, thus suggesting its participation in the defense system and nociception modulation.The elevated plus maze (EPM) is an apparatus used to assess rodent anxiety and it is sensitive to anxiolytic and anxiogenic effect of drugs. In this sense, EPM is used to study the neurobiology of antinociception induced by the aversive potential of the open arms experiment. Thus, considering evidences of the antiaversive role of serotonin in the amygdala, observed with chronic treatment with serotonin reuptake inhibitors, this study aimed to evaluate the role of amygdala 5-HT1A and 5-HT2C serotonin receptor subtypes on nociception and antinociception effects of mice exposed to the EPM in this context. For this, 5-HT1A (8-OH-DPAT) and 5-HT2C (MK-212) receptor agonists were microinjected intra-amygdala associated with chronic systemic treatment of fluoxetine in mice. The animals were confined in the enclosed or open arm of the EPM and the number of abdominal writings after the intraperitoneal (i.p.) injection of acetic acid solution was counted. Intra-amygdala treatment with 8-OH-DPAT produced an increase in the number of writhes in both mice that were confined in the open arm and those that were confined in the enclosed arm. However, treatment fluoxetine + 8-OH-DPAT blocked the effect of intra-amygdala injection only for the mice confined in the open arm. Intra-amygdala treatment with MK-212 produced a decrease in the number of writhes only in mice that were confined to the open arm, and the fluoxetine + MK-212 treatment impaired this effect. These results suggest that chronic treatment with fluoxetine reversed the effects produced by the activation of the 5-HT1A and 5-HT2C receptors in the amygdala of mice confined to the EPM.Estudos apontam que quadros de ansiedade e depressão podem ser acompanhados por sintomas de dor intensa sem localização precisa ou lesões aparentes, e diversas evidências demonstram que alguns fármacos antidepressivos utilizados no tratamento destes transtornos emocionais também são eficazes no alívio da dor. Sendo a interação entre estas respostas emocionais e sensoriais de alta relevância para a sobrevivência das espécies, diversos trabalhos têm demonstrado que a exposição a situações ameaçadoras, resulta em reações comportamentais e fisiológicas de defesa que são acompanhadas por inibição da dor. A amídala, um complexo subcortical de núcleos, tem se mostrado envolvida no mecanismo da antinocicepção induzida pelo medo, além de ser um complexo de interface entre os estímulos sensoriais e emocionais, e evidências tem demonstrado que a estimulação desta estrutura pode induzir reações de medo ou ansiedade, acompanhada por analgesia, sugerindo assim sua participação no sistema de defesa e na modulação da nocicepção. Neste sentido, o labirinto em cruz elevado (LCE), um aparato utilizado para avaliar ansiedade em roedores, sensível ao efeito ansiolítico e ansiogênico de drogas, é também utilizado ao estudo da neurobiologia da antinocicepção induzida pelo potencial aversivo da experiência nos braços abertos. Assim, considerando evidências do papel antiaversivo da serotonina na amídala, observado com o tratamento crônico com inibidores da recaptação de serotonina, este estudo teve por objetivo avaliar o papel dos subtipos de receptores serotonérgicos 5-HT1A e 5-HT2C da amídala sobre a nocicepção e antinocicepção de camundongos expostos ao LCE. Para isso, utilizamos administração intra-amídala de agonistas dos receptores 5HT1A (8-OH-DPAT) e 5HT2C (MK-212), após o tratamento sistêmico crônico, de fluoxetina em camundongos. Os animais foram confinados no braço fechado ou aberto do LCE e foi avaliado o número de contorções abdominais após a injeção intraperitonial (i.p.) de solução de acido acético. O tratamento intra-amídala com 8-OH-DPAT produziu um aumento no número de contorções tanto nos camundongos que foram confinados no braço aberto quanto nos que foram confinados no braço fechado. Entretanto, o tratamento fluoxetina+8-OH-DPAT bloqueou esse efeito da injeção intra-amídala somente para os camundongos confinados no braço aberto. O tratamento intra-amídala com MK-212 produziu uma diminuição no número de contorções somente nos camundongos que foram confinados no braço aberto, e o tratamento fluoxetina+MK-212 prejudicou esse efeito. Diante destes resultados, é possível sugerir que o tratamento crônico com a fluoxetina reverte os efeitos produzidos pela ativação dos receptores 5-HT1A e 5-HT2C da amidala de camundongos confinados ao LCE.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)CAPES: Código de Financiamento 001porUniversidade Federal de São CarlosCâmpus São CarlosPrograma Interinstitucional de Pós-Graduação em Ciências Fisiológicas - PIPGCFUFSCarAntinocicepçãoLabirinto em cruz elevadoSerotoninaFluoxetinaAmidalaCamundongosAntinociceptionElevated plus mazeSerotoninFluoxetineAmygdalaMiceCIENCIAS BIOLOGICAS::FISIOLOGIA::FISIOLOGIA DE ORGAOS E SISTEMAS::NEUROFISIOLOGIAO tratamento crônico com fluoxetina reverte os efeitos nociceptivo e antinociceptivo induzidos pela ativação dos receptores 5-HT1A e 5-HT2C da amídala de camundongos confinados aos braços do labirinto em cruz elevadoChronic fluoxetine treatment reverse nociceptive and antinociceptive effects induced by activation of the 5-HT1A and 5-HT2C amygdala receptors of confined mice to elevated plus mazeinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisOnline600ec59bf11-8f1b-4d55-a0dd-35037d3bb124info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINALTese Elke versao final.pdfTese Elke versao final.pdfapplication/pdf1118170https://repositorio.ufscar.br/bitstream/ufscar/11752/1/Tese%20Elke%20versao%20final.pdf633e88e8582e912b1e9162289d715973MD51LICENSElicense.txtlicense.txttext/plain; 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dc.title.por.fl_str_mv O tratamento crônico com fluoxetina reverte os efeitos nociceptivo e antinociceptivo induzidos pela ativação dos receptores 5-HT1A e 5-HT2C da amídala de camundongos confinados aos braços do labirinto em cruz elevado
dc.title.alternative.eng.fl_str_mv Chronic fluoxetine treatment reverse nociceptive and antinociceptive effects induced by activation of the 5-HT1A and 5-HT2C amygdala receptors of confined mice to elevated plus maze
title O tratamento crônico com fluoxetina reverte os efeitos nociceptivo e antinociceptivo induzidos pela ativação dos receptores 5-HT1A e 5-HT2C da amídala de camundongos confinados aos braços do labirinto em cruz elevado
spellingShingle O tratamento crônico com fluoxetina reverte os efeitos nociceptivo e antinociceptivo induzidos pela ativação dos receptores 5-HT1A e 5-HT2C da amídala de camundongos confinados aos braços do labirinto em cruz elevado
Furuya-da-Cunha, Elke Mayumi
Antinocicepção
Labirinto em cruz elevado
Serotonina
Fluoxetina
Amidala
Camundongos
Antinociception
Elevated plus maze
Serotonin
Fluoxetine
Amygdala
Mice
CIENCIAS BIOLOGICAS::FISIOLOGIA::FISIOLOGIA DE ORGAOS E SISTEMAS::NEUROFISIOLOGIA
title_short O tratamento crônico com fluoxetina reverte os efeitos nociceptivo e antinociceptivo induzidos pela ativação dos receptores 5-HT1A e 5-HT2C da amídala de camundongos confinados aos braços do labirinto em cruz elevado
title_full O tratamento crônico com fluoxetina reverte os efeitos nociceptivo e antinociceptivo induzidos pela ativação dos receptores 5-HT1A e 5-HT2C da amídala de camundongos confinados aos braços do labirinto em cruz elevado
title_fullStr O tratamento crônico com fluoxetina reverte os efeitos nociceptivo e antinociceptivo induzidos pela ativação dos receptores 5-HT1A e 5-HT2C da amídala de camundongos confinados aos braços do labirinto em cruz elevado
title_full_unstemmed O tratamento crônico com fluoxetina reverte os efeitos nociceptivo e antinociceptivo induzidos pela ativação dos receptores 5-HT1A e 5-HT2C da amídala de camundongos confinados aos braços do labirinto em cruz elevado
title_sort O tratamento crônico com fluoxetina reverte os efeitos nociceptivo e antinociceptivo induzidos pela ativação dos receptores 5-HT1A e 5-HT2C da amídala de camundongos confinados aos braços do labirinto em cruz elevado
author Furuya-da-Cunha, Elke Mayumi
author_facet Furuya-da-Cunha, Elke Mayumi
author_role author
dc.contributor.authorlattes.por.fl_str_mv http://lattes.cnpq.br/9582420020561046
dc.contributor.author.fl_str_mv Furuya-da-Cunha, Elke Mayumi
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 c338a839-5bcb-4d08-bd3c-e45ce7af230b
contributor_str_mv Souza, Azair Liane Matos do Canto de
dc.subject.por.fl_str_mv Antinocicepção
Labirinto em cruz elevado
Serotonina
Fluoxetina
Amidala
Camundongos
topic Antinocicepção
Labirinto em cruz elevado
Serotonina
Fluoxetina
Amidala
Camundongos
Antinociception
Elevated plus maze
Serotonin
Fluoxetine
Amygdala
Mice
CIENCIAS BIOLOGICAS::FISIOLOGIA::FISIOLOGIA DE ORGAOS E SISTEMAS::NEUROFISIOLOGIA
dc.subject.eng.fl_str_mv Antinociception
Elevated plus maze
Serotonin
Fluoxetine
Amygdala
Mice
dc.subject.cnpq.fl_str_mv CIENCIAS BIOLOGICAS::FISIOLOGIA::FISIOLOGIA DE ORGAOS E SISTEMAS::NEUROFISIOLOGIA
description Several studies indicate that anxiety and depression may be accompanied by symptoms of severe pain with no precise location or apparent lesions. Several evidences demonstrate that some antidepressive drugs used in the treatment of these emotional disorders are also effective in the relief of pain. The interaction between emotional and sensorial responses is of high relevance for the survival of the species. Several studies have shown that exposure to threatening situations results in behavioral and physiological defense reactions that be accompanied by inhibition of pain. The amygdala, a subcortical nucleus complex, has been shown to be involved in the mechanism of fear-induced antinociception. And it being a complex of interface between the sensorial and emotional stimuli. Evidences have shown that stimulation of this structure can induce fear or anxiety reactions, accompanied by analgesia, thus suggesting its participation in the defense system and nociception modulation.The elevated plus maze (EPM) is an apparatus used to assess rodent anxiety and it is sensitive to anxiolytic and anxiogenic effect of drugs. In this sense, EPM is used to study the neurobiology of antinociception induced by the aversive potential of the open arms experiment. Thus, considering evidences of the antiaversive role of serotonin in the amygdala, observed with chronic treatment with serotonin reuptake inhibitors, this study aimed to evaluate the role of amygdala 5-HT1A and 5-HT2C serotonin receptor subtypes on nociception and antinociception effects of mice exposed to the EPM in this context. For this, 5-HT1A (8-OH-DPAT) and 5-HT2C (MK-212) receptor agonists were microinjected intra-amygdala associated with chronic systemic treatment of fluoxetine in mice. The animals were confined in the enclosed or open arm of the EPM and the number of abdominal writings after the intraperitoneal (i.p.) injection of acetic acid solution was counted. Intra-amygdala treatment with 8-OH-DPAT produced an increase in the number of writhes in both mice that were confined in the open arm and those that were confined in the enclosed arm. However, treatment fluoxetine + 8-OH-DPAT blocked the effect of intra-amygdala injection only for the mice confined in the open arm. Intra-amygdala treatment with MK-212 produced a decrease in the number of writhes only in mice that were confined to the open arm, and the fluoxetine + MK-212 treatment impaired this effect. These results suggest that chronic treatment with fluoxetine reversed the effects produced by the activation of the 5-HT1A and 5-HT2C receptors in the amygdala of mice confined to the EPM.
publishDate 2019
dc.date.accessioned.fl_str_mv 2019-08-20T14:57:09Z
dc.date.available.fl_str_mv 2019-08-20T14:57:09Z
dc.date.issued.fl_str_mv 2019-05-31
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.citation.fl_str_mv FURUYA-DA-CUNHA, Elke Mayumi. O tratamento crônico com fluoxetina reverte os efeitos nociceptivo e antinociceptivo induzidos pela ativação dos receptores 5-HT1A e 5-HT2C da amídala de camundongos confinados aos braços do labirinto em cruz elevado. 2019. Tese (Doutorado em Ciências Fisiológicas) – Universidade Federal de São Carlos, São Carlos, 2019. Disponível em: https://repositorio.ufscar.br/handle/ufscar/11752.
dc.identifier.uri.fl_str_mv https://repositorio.ufscar.br/handle/ufscar/11752
identifier_str_mv FURUYA-DA-CUNHA, Elke Mayumi. O tratamento crônico com fluoxetina reverte os efeitos nociceptivo e antinociceptivo induzidos pela ativação dos receptores 5-HT1A e 5-HT2C da amídala de camundongos confinados aos braços do labirinto em cruz elevado. 2019. Tese (Doutorado em Ciências Fisiológicas) – Universidade Federal de São Carlos, São Carlos, 2019. Disponível em: https://repositorio.ufscar.br/handle/ufscar/11752.
url https://repositorio.ufscar.br/handle/ufscar/11752
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language por
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dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Universidade Federal de São Carlos
Câmpus São Carlos
dc.publisher.program.fl_str_mv Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas - PIPGCF
dc.publisher.initials.fl_str_mv UFSCar
publisher.none.fl_str_mv Universidade Federal de São Carlos
Câmpus São Carlos
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFSCAR
instname:Universidade Federal de São Carlos (UFSCAR)
instacron:UFSCAR
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institution UFSCAR
reponame_str Repositório Institucional da UFSCAR
collection Repositório Institucional da UFSCAR
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bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
repository.name.fl_str_mv Repositório Institucional da UFSCAR - Universidade Federal de São Carlos (UFSCAR)
repository.mail.fl_str_mv
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