Investiga??o da participa??o dos receptores serotonin?rgicos 5-HT5A, 5-HT6 e 5-HT7 na extin??o da mem?ria de medo condicionado ao contexto

Detalhes bibliográficos
Autor(a) principal: Assis Brasil, Eduardo Silva de
Data de Publicação: 2019
Tipo de documento: Tese
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da PUC_RS
Texto Completo: http://tede2.pucrs.br/tede2/handle/tede/8817
Resumo: Fear memories can lead to exaggerated defensive behavior in response to threats, such as Post Traumatic Stress Disorder (PTSD). Extinction is the learned inhibition of retrieval, it may be useful in restricting the expression of fear memories to appropriate situations. The hippocampus and basolateral amygdala (ABL) are essential for extinction to occur. This process can be modulated by different drugs and neurotransmitters, for example, serotonin. The serotonergic system has receptors located in several areas in the brain and its role is well documented in various behavioral tasks. It is known that the most recently described receptors 5-HT5A, 5-HT6 and 5-HT7 are related to the formation of some types of memory, however the role of these receptors in the process of extinction of fear memory remains unknown. Therefore, this study aims to investigate the role of 5-HT5A, 5-HT6 and 5-HT7 receptors in the extinction of context-conditioned fear memory. For this, male Wistar rats with cannulas implanted in the CA1 region of the hippocampus or ABL were submitted to the context-dependent fear memory extinction protocol and received infusions of agonists and antagonists of the 5-HT5A, 5-HT6 and 5-HT7 receptors immediately or 3 hours after extinction and tested 24 hours later. When the drugs were infused in CA1 immediately or 3 h after extinction training, the animals did not present difference in relation to the control group. However, when 5-HT5A and 5-HT7 receptor antagonists were infused immediately or 3 h after extinction training in the ABL, the process of extinction was facilitated, this effect was also seen when infused 5-HT6 antagonist only immediately after extinction training in the ABL, the groups that received the agonists of these receptors did not differ from the control group. In summary, the antagonists of the 5-HT5A, 5-HT6 and 5-HT7 receptors in the ABL, but not in the CA1 region of the hippocampus, was able to facilitate de extinction consolidation.
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spelling Izquierdo, Ivan Ant?niohttp://lattes.cnpq.br/0862583266198572Myskiw, Jociane de Carvalhohttp://lattes.cnpq.br/3146559515066831http://lattes.cnpq.br/0083548647213078Assis Brasil, Eduardo Silva de2019-07-26T11:33:41Z2019-02-26http://tede2.pucrs.br/tede2/handle/tede/8817Fear memories can lead to exaggerated defensive behavior in response to threats, such as Post Traumatic Stress Disorder (PTSD). Extinction is the learned inhibition of retrieval, it may be useful in restricting the expression of fear memories to appropriate situations. The hippocampus and basolateral amygdala (ABL) are essential for extinction to occur. This process can be modulated by different drugs and neurotransmitters, for example, serotonin. The serotonergic system has receptors located in several areas in the brain and its role is well documented in various behavioral tasks. It is known that the most recently described receptors 5-HT5A, 5-HT6 and 5-HT7 are related to the formation of some types of memory, however the role of these receptors in the process of extinction of fear memory remains unknown. Therefore, this study aims to investigate the role of 5-HT5A, 5-HT6 and 5-HT7 receptors in the extinction of context-conditioned fear memory. For this, male Wistar rats with cannulas implanted in the CA1 region of the hippocampus or ABL were submitted to the context-dependent fear memory extinction protocol and received infusions of agonists and antagonists of the 5-HT5A, 5-HT6 and 5-HT7 receptors immediately or 3 hours after extinction and tested 24 hours later. When the drugs were infused in CA1 immediately or 3 h after extinction training, the animals did not present difference in relation to the control group. However, when 5-HT5A and 5-HT7 receptor antagonists were infused immediately or 3 h after extinction training in the ABL, the process of extinction was facilitated, this effect was also seen when infused 5-HT6 antagonist only immediately after extinction training in the ABL, the groups that received the agonists of these receptors did not differ from the control group. In summary, the antagonists of the 5-HT5A, 5-HT6 and 5-HT7 receptors in the ABL, but not in the CA1 region of the hippocampus, was able to facilitate de extinction consolidation.As mem?rias de medo podem levar a comportamentos defensivos exagerados em resposta a amea?as, como ocorre no Transtorno de Estresse P?s-Traum?tico (TEPT). A extin??o, novo aprendizado que se sobrep?e ? mem?ria original e inibe sua evoca??o, pode ser ?til para restringir a express?o das mem?rias de medo a situa??es adequadas. O hipocampo e a am?gdala basolateral (ABL) s?o estruturas essenciais para que ocorra a extin??o. Esse processo pode ser modulado por diferentes f?rmacos e neurotransmissores, como por exemplo, a serotonina. O sistema serotonin?rgico possui receptores localizados em diversas ?reas no c?rebro e seu papel ? bem documentado em diversas tarefas comportamentais. Sabe-se que os receptores mais recentementes descritos 5-HT5A, 5-HT6 e 5-HT7 est?o relacionados com a forma??o de alguns tipos de mem?ria, entretanto nada se sabe sobre a participa??o desses receptores no processo de extin??o da mem?ria de medo. Portanto este estudo visa investigar o papel dos receptores 5-HT5A, 5-HT6 e 5-HT7 na extin??o da mem?ria de medo condicionada ao contexto. Para isso, ratos Wistar machos com c?nulas implantadas na regi?o de CA1 do hipocampo ou ABL foram submetidos ao protocolo de extin??o da mem?ria de medo condicionado ao contexto e receberam infus?es de agonistas e antagonistas dos receptores 5-HT5A, 5-HT6 e 5-HT7 imediatamente ou 3h ap?s a extin??o e testados 24h depois. Quando os farmacos foram infundidos em CA1 imediatamente ou 3h ap?s a extin??o, os animais n?o apresentaram diferen?a em rela??o ao grupo controle. Entretanto, quando os antagonistas dos receptores 5-HT5A e 5-HT7 foram infundidos imediatamente ou 3h ap?s a extin??o na ABL foi visto uma facilita??o no processo de extin??o, esse efeito tamb?m foi visto quando infundido o antagonista 5-HT6 apenas imediatamente ap?s a extin??o na ABL, j? os grupos que receberam os agonistas desses receptores n?o foram diferentes do grupo controle. Concluindo, o bloqueio dos receptores 5-HT5A, 5-HT6 e 5-HT7 na ABL, mas n?o na regi?o CA1 do hipocampo, foi capaz de facilitar a consolida??o da extin??o.Submitted by PPG Medicina e Ci?ncias da Sa?de (medicina-pg@pucrs.br) on 2019-07-19T14:40:59Z No. of bitstreams: 1 Eduardo_Silva_de_Assis_Brasil.pdf: 1983681 bytes, checksum: 877de02a69def13b80d716ab296cd04f (MD5)Approved for entry into archive by Sarajane Pan (sarajane.pan@pucrs.br) on 2019-07-26T11:23:31Z (GMT) No. of bitstreams: 1 Eduardo_Silva_de_Assis_Brasil.pdf: 1983681 bytes, checksum: 877de02a69def13b80d716ab296cd04f (MD5)Made available in DSpace on 2019-07-26T11:33:41Z (GMT). No. of bitstreams: 1 Eduardo_Silva_de_Assis_Brasil.pdf: 1983681 bytes, checksum: 877de02a69def13b80d716ab296cd04f (MD5) Previous issue date: 2019-02-26Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPESapplication/pdfhttp://tede2.pucrs.br:80/tede2/retrieve/176035/Eduardo_Silva_de_Assis_Brasil.pdf.jpgporPontif?cia Universidade Cat?lica do Rio Grande do SulPrograma de P?s-Gradua??o em Medicina e Ci?ncias da Sa?dePUCRSBrasilEscola de MedicinaMem?riaMedo Condicionado ao ContextoExtin??oSerotoninaHipocampoAm?gdalaMemoryConditioned FearExtinctionSerotoninHippocampusAmygdalaCIENCIAS DA SAUDE::MEDICINAInvestiga??o da participa??o dos receptores serotonin?rgicos 5-HT5A, 5-HT6 e 5-HT7 na extin??o da mem?ria de medo condicionado ao contextoinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisTrabalho n?o apresenta restri??o para publica??o-721401722658532398500500500600-224747486637135387-9693694523087866273590462550136975366info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da PUC_RSinstname:Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)instacron:PUC_RSTHUMBNAILEduardo_Silva_de_Assis_Brasil.pdf.jpgEduardo_Silva_de_Assis_Brasil.pdf.jpgimage/jpeg5539http://tede2.pucrs.br/tede2/bitstream/tede/8817/4/Eduardo_Silva_de_Assis_Brasil.pdf.jpgb3e5ea27e6c65b4c8c8adf238ebc1c90MD54TEXTEduardo_Silva_de_Assis_Brasil.pdf.txtEduardo_Silva_de_Assis_Brasil.pdf.txttext/plain134643http://tede2.pucrs.br/tede2/bitstream/tede/8817/3/Eduardo_Silva_de_Assis_Brasil.pdf.txtc507b9d2cf4bf5f6ad7e8e97fd1a3f7cMD53ORIGINALEduardo_Silva_de_Assis_Brasil.pdfEduardo_Silva_de_Assis_Brasil.pdfapplication/pdf1983681http://tede2.pucrs.br/tede2/bitstream/tede/8817/2/Eduardo_Silva_de_Assis_Brasil.pdf877de02a69def13b80d716ab296cd04fMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-8590http://tede2.pucrs.br/tede2/bitstream/tede/8817/1/license.txt220e11f2d3ba5354f917c7035aadef24MD51tede/88172019-07-26 12:00:30.058oai:tede2.pucrs.br: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Biblioteca Digital de Teses e Dissertaçõeshttp://tede2.pucrs.br/tede2/PRIhttps://tede2.pucrs.br/oai/requestbiblioteca.central@pucrs.br||opendoar:2019-07-26T15:00:30Biblioteca Digital de Teses e Dissertações da PUC_RS - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)false
dc.title.por.fl_str_mv Investiga??o da participa??o dos receptores serotonin?rgicos 5-HT5A, 5-HT6 e 5-HT7 na extin??o da mem?ria de medo condicionado ao contexto
title Investiga??o da participa??o dos receptores serotonin?rgicos 5-HT5A, 5-HT6 e 5-HT7 na extin??o da mem?ria de medo condicionado ao contexto
spellingShingle Investiga??o da participa??o dos receptores serotonin?rgicos 5-HT5A, 5-HT6 e 5-HT7 na extin??o da mem?ria de medo condicionado ao contexto
Assis Brasil, Eduardo Silva de
Mem?ria
Medo Condicionado ao Contexto
Extin??o
Serotonina
Hipocampo
Am?gdala
Memory
Conditioned Fear
Extinction
Serotonin
Hippocampus
Amygdala
CIENCIAS DA SAUDE::MEDICINA
title_short Investiga??o da participa??o dos receptores serotonin?rgicos 5-HT5A, 5-HT6 e 5-HT7 na extin??o da mem?ria de medo condicionado ao contexto
title_full Investiga??o da participa??o dos receptores serotonin?rgicos 5-HT5A, 5-HT6 e 5-HT7 na extin??o da mem?ria de medo condicionado ao contexto
title_fullStr Investiga??o da participa??o dos receptores serotonin?rgicos 5-HT5A, 5-HT6 e 5-HT7 na extin??o da mem?ria de medo condicionado ao contexto
title_full_unstemmed Investiga??o da participa??o dos receptores serotonin?rgicos 5-HT5A, 5-HT6 e 5-HT7 na extin??o da mem?ria de medo condicionado ao contexto
title_sort Investiga??o da participa??o dos receptores serotonin?rgicos 5-HT5A, 5-HT6 e 5-HT7 na extin??o da mem?ria de medo condicionado ao contexto
author Assis Brasil, Eduardo Silva de
author_facet Assis Brasil, Eduardo Silva de
author_role author
dc.contributor.advisor1.fl_str_mv Izquierdo, Ivan Ant?nio
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/0862583266198572
dc.contributor.advisor-co1.fl_str_mv Myskiw, Jociane de Carvalho
dc.contributor.advisor-co1Lattes.fl_str_mv http://lattes.cnpq.br/3146559515066831
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/0083548647213078
dc.contributor.author.fl_str_mv Assis Brasil, Eduardo Silva de
contributor_str_mv Izquierdo, Ivan Ant?nio
Myskiw, Jociane de Carvalho
dc.subject.por.fl_str_mv Mem?ria
Medo Condicionado ao Contexto
Extin??o
Serotonina
Hipocampo
Am?gdala
topic Mem?ria
Medo Condicionado ao Contexto
Extin??o
Serotonina
Hipocampo
Am?gdala
Memory
Conditioned Fear
Extinction
Serotonin
Hippocampus
Amygdala
CIENCIAS DA SAUDE::MEDICINA
dc.subject.eng.fl_str_mv Memory
Conditioned Fear
Extinction
Serotonin
Hippocampus
Amygdala
dc.subject.cnpq.fl_str_mv CIENCIAS DA SAUDE::MEDICINA
description Fear memories can lead to exaggerated defensive behavior in response to threats, such as Post Traumatic Stress Disorder (PTSD). Extinction is the learned inhibition of retrieval, it may be useful in restricting the expression of fear memories to appropriate situations. The hippocampus and basolateral amygdala (ABL) are essential for extinction to occur. This process can be modulated by different drugs and neurotransmitters, for example, serotonin. The serotonergic system has receptors located in several areas in the brain and its role is well documented in various behavioral tasks. It is known that the most recently described receptors 5-HT5A, 5-HT6 and 5-HT7 are related to the formation of some types of memory, however the role of these receptors in the process of extinction of fear memory remains unknown. Therefore, this study aims to investigate the role of 5-HT5A, 5-HT6 and 5-HT7 receptors in the extinction of context-conditioned fear memory. For this, male Wistar rats with cannulas implanted in the CA1 region of the hippocampus or ABL were submitted to the context-dependent fear memory extinction protocol and received infusions of agonists and antagonists of the 5-HT5A, 5-HT6 and 5-HT7 receptors immediately or 3 hours after extinction and tested 24 hours later. When the drugs were infused in CA1 immediately or 3 h after extinction training, the animals did not present difference in relation to the control group. However, when 5-HT5A and 5-HT7 receptor antagonists were infused immediately or 3 h after extinction training in the ABL, the process of extinction was facilitated, this effect was also seen when infused 5-HT6 antagonist only immediately after extinction training in the ABL, the groups that received the agonists of these receptors did not differ from the control group. In summary, the antagonists of the 5-HT5A, 5-HT6 and 5-HT7 receptors in the ABL, but not in the CA1 region of the hippocampus, was able to facilitate de extinction consolidation.
publishDate 2019
dc.date.accessioned.fl_str_mv 2019-07-26T11:33:41Z
dc.date.issued.fl_str_mv 2019-02-26
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