Estudo comportamental e neuroquímico em ratos periadolescentes submetidos ao tratamento agudo e subcrônico com efavirenz

Detalhes bibliográficos
Ano de defesa: 2011
Autor(a) principal: Cavalcante, Giuliana Ignácio Teixeira
Orientador(a): Fonteles, Marta Maria de França
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/15655
Resumo: Antiretroviral therapy has revolutionized the treatment of patients infected with human immunodeficiency virus (HIV) because it improved the clinical status of these patients. It is essential that at least one of the drugs used and in this therapy cross the blood-brain barrier, since HIV reaches the central nervous system (CNS), causing damage. Efavirenz is an antiretroviral widely used in HIV and able to cross the blood-brain barrier. However, patients treated with efavirenz are presenting neuropsychiatric disorders such as depression, anxiety, mania, suicidal thoughts, psychosis and hallucinations. Based on these facts, this study aimed to assess whether the behavioral changes anxiety, depression and seizures induced by pilocarpine occur in animals treated with efavirenz with a single dose and for a period of 15 days, using standard models of animal behavior as well as check if the treatment with drug can cause changes in monoamines and amino acids. We used male Wistar rats (35 days, n = 6-8). The animals were treated once with efavirenz in the case of an acute treatment, or 15 days for a subchronic treatment. The treated animals and controls were tested for behavioral elevated plus maze (Plus Maze), Forced Swim, Open Field and seizure induced by pilocarpine. To assess neurochemistry, mice were sacrificed and the brain was removed for the analysis of the following areas of interest: striatum, prefrontal cortex and hippocampus. Were measured monoamines and their metabolites, amino acids and the levels of malondialdehyde (MDA). The results showed that efavirenz caused anxiety and motor abnormalities similar to psychogenic drugs in behavioral tests after acute administration, caused depression in the behavioral test after subchronic treatment, had no effect on the latency of convulsion, altered monoamine metabolites and increased levels MDA. Thus, it is conclude that efavirenz, according to this study, promotes neurochemical changes in the central nervous system, causing neuropsychiatric disorders.
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spelling Cavalcante, Giuliana Ignácio TeixeiraFonteles, Marta Maria de França2016-03-22T13:26:43Z2016-03-22T13:26:43Z2011CAVALCANTE, G. I, T. Estudo comportamental e neuroquímico em ratos periadolescentes submetidos ao tratamento agudo e subcrônico com efavirenz. 2011. 121 f. Dissertação (Mestrado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2011.http://www.repositorio.ufc.br/handle/riufc/15655Antiretroviral therapy has revolutionized the treatment of patients infected with human immunodeficiency virus (HIV) because it improved the clinical status of these patients. It is essential that at least one of the drugs used and in this therapy cross the blood-brain barrier, since HIV reaches the central nervous system (CNS), causing damage. Efavirenz is an antiretroviral widely used in HIV and able to cross the blood-brain barrier. However, patients treated with efavirenz are presenting neuropsychiatric disorders such as depression, anxiety, mania, suicidal thoughts, psychosis and hallucinations. Based on these facts, this study aimed to assess whether the behavioral changes anxiety, depression and seizures induced by pilocarpine occur in animals treated with efavirenz with a single dose and for a period of 15 days, using standard models of animal behavior as well as check if the treatment with drug can cause changes in monoamines and amino acids. We used male Wistar rats (35 days, n = 6-8). The animals were treated once with efavirenz in the case of an acute treatment, or 15 days for a subchronic treatment. The treated animals and controls were tested for behavioral elevated plus maze (Plus Maze), Forced Swim, Open Field and seizure induced by pilocarpine. To assess neurochemistry, mice were sacrificed and the brain was removed for the analysis of the following areas of interest: striatum, prefrontal cortex and hippocampus. Were measured monoamines and their metabolites, amino acids and the levels of malondialdehyde (MDA). The results showed that efavirenz caused anxiety and motor abnormalities similar to psychogenic drugs in behavioral tests after acute administration, caused depression in the behavioral test after subchronic treatment, had no effect on the latency of convulsion, altered monoamine metabolites and increased levels MDA. Thus, it is conclude that efavirenz, according to this study, promotes neurochemical changes in the central nervous system, causing neuropsychiatric disorders.A terapia antirretroviral revolucionou o tratamento dos pacientes portadores do vírus da imunodeficiência humana (HIV) porque melhorou o estado clínico destes pacientes. É essencial que no mínimo uma das drogas utilizadas nesta terapia atravesse bem a barreira hemato-encefálica, já que o HIV alcança o sistema nervoso central (SNC), causando danos. O Efavirenz é um antirretroviral capaz de atravessar bem a barreira hemato-encefálica, sendo bastante utilizado no tratamento para HIV. Entretanto, pacientes tratados com Efavirenz vêm apresentando alterações neuropsiquiátricas como depressão, ansiedade, mania, pensamentos suicidas, psicoses e alucinações. Baseado nestes fatos, o presente estudo objetivou avaliar se as alterações comportamentais ansiedade, depressão e convulsão ocorrem em animais tratados com Efavirenz com uma única dose e por um período de 15 dias, através de modelos padronizados de comportamento animal, bem como verificar se o tratamento com o fármaco é capaz de causar alterações de monoaminas e de aminoácidos. Foram utilizados ratos Wistar machos (35 dias, n=6-8). Os animais foram tratados uma única vez com efavirenz, no caso do tratamento agudo, ou por 15 dias, para o tratamento subcrônico. Os animais tratados e controles foram submetidos aos testes comportamentais de Labirinto em Cruz Elevado (Plus Maze), Nado Forçado, Campo Aberto e Convulsão induzida por pilocarpina. Para a avaliação neuroquímica, as cobaias foram sacrificadas e o cérebro foi removido para análise das seguintes áreas de interesse: corpo estriado, córtex pré-frontal e hipocampo. Foram dosadas as monoaminas e seus metabólitos, os aminoácidos e os níveis de malonildialdeído (MDA). Os resultados mostraram que o Efavirenz ocasionou, nos testes comportamentais, ansiedade após administração aguda, causou depressão no teste comportamental após tratamento subcrônico, não interferiu na latência de convulsão e alterou monoaminas e metabólitos, além de elevar os níveis de MDA. Desse modo, conclui-se que o efavirenz, de acordo com este estudo, promove alterações neuroquímicas no sistema nervoso central causando distúrbios neuropsiquiátricos.Transtornos MentaisSistema Nervoso CentralEfeitos AdversosEstudo comportamental e neuroquímico em ratos periadolescentes submetidos ao tratamento agudo e subcrônico com efavirenzBehavioral and neurochemical study in periadolescent rats submitted to acute and subchronic treatment with efavirenzinfo: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/openAccessORIGINAL2011_dis_gitcavalcante.pdf2011_dis_gitcavalcante.pdfapplication/pdf805689http://repositorio.ufc.br/bitstream/riufc/15655/1/2011_dis_gitcavalcante.pdf1484b0eca40b18d34ac122bd7d1bcca6MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81786http://repositorio.ufc.br/bitstream/riufc/15655/2/license.txt8c4401d3d14722a7ca2d07c782a1aab3MD52riufc/156552021-06-16 09:17:15.898oai:repositorio.ufc.br:riufc/15655w4kgbmVjZXNzw6FyaW8gY29uY29yZGFyIGNvbSBhIGxpY2Vuw6dhIGRlIGRpc3RyaWJ1acOnw6NvIG7Do28tZXhjbHVzaXZhLAphbnRlcyBxdWUgbyBkb2N1bWVudG8gcG9zc2EgYXBhcmVjZXIgbm8gUmVwb3NpdMOzcmlvLiBQb3IgZmF2b3IsIGxlaWEgYQpsaWNlbsOnYSBhdGVudGFtZW50ZS4gQ2FzbyBuZWNlc3NpdGUgZGUgYWxndW0gZXNjbGFyZWNpbWVudG8gZW50cmUgZW0KY29udGF0byBhdHJhdsOpcyBkZTogcmVwb3NpdG9yaW9AdWZjLmJyIG91ICg4NSkzMzY2LTk1MDguCgpMSUNFTsOHQSBERSBESVNUUklCVUnDh8ODTyBOw4NPLUVYQ0xVU0lWQQoKQW8gYXNzaW5hciBlIGVudHJlZ2FyIGVzdGEgbGljZW7Dp2EsIG8vYSBTci4vU3JhLiAoYXV0b3Igb3UgZGV0ZW50b3IgZG9zIGRpcmVpdG9zIGRlIGF1dG9yKToKCmEpIENvbmNlZGUgw6AgVW5pdmVyc2lkYWRlIEZlZGVyYWwgZG8gQ2VhcsOhIG8gZGlyZWl0byBuw6NvLWV4Y2x1c2l2byBkZQpyZXByb2R1emlyLCBjb252ZXJ0ZXIgKGNvbW8gZGVmaW5pZG8gYWJhaXhvKSwgY29tdW5pY2FyIGUvb3UKZGlzdHJpYnVpciBvIGRvY3VtZW50byBlbnRyZWd1ZSAoaW5jbHVpbmRvIG8gcmVzdW1vL2Fic3RyYWN0KSBlbQpmb3JtYXRvIGRpZ2l0YWwgb3UgaW1wcmVzc28gZSBlbSBxdWFscXVlciBtZWlvLgoKYikgRGVjbGFyYSBxdWUgbyBkb2N1bWVudG8gZW50cmVndWUgw6kgc2V1IHRyYWJhbGhvIG9yaWdpbmFsLCBlIHF1ZQpkZXTDqW0gbyBkaXJlaXRvIGRlIGNvbmNlZGVyIG9zIGRpcmVpdG9zIGNvbnRpZG9zIG5lc3RhIGxpY2Vuw6dhLiBEZWNsYXJhIHRhbWLDqW0gcXVlIGEgZW50cmVnYSBkbyBkb2N1bWVudG8gbsOjbyBpbmZyaW5nZSwgdGFudG8gcXVhbnRvIGxoZSDDqSBwb3Nzw612ZWwgc2FiZXIsIG9zIGRpcmVpdG9zIGRlIHF1YWxxdWVyIG91dHJhIHBlc3NvYSBvdSBlbnRpZGFkZS4KCmMpIFNlIG8gZG9jdW1lbnRvIGVudHJlZ3VlIGNvbnTDqW0gbWF0ZXJpYWwgZG8gcXVhbCBuw6NvIGRldMOpbSBvcwpkaXJlaXRvcyBkZSBhdXRvciwgZGVjbGFyYSBxdWUgb2J0ZXZlIGF1dG9yaXphw6fDo28gZG8gZGV0ZW50b3IgZG9zCmRpcmVpdG9zIGRlIGF1dG9yIHBhcmEgY29uY2VkZXIgw6AgVW5pdmVyc2lkYWRlIEZlZGVyYWwgZG8gQ2VhcsOhIG9zIGRpcmVpdG9zIHJlcXVlcmlkb3MgcG9yIGVzdGEgbGljZW7Dp2EsIGUgcXVlIGVzc2UgbWF0ZXJpYWwgY3Vqb3MgZGlyZWl0b3Mgc8OjbyBkZSB0ZXJjZWlyb3MgZXN0w6EgY2xhcmFtZW50ZSBpZGVudGlmaWNhZG8gZSByZWNvbmhlY2lkbyBubyB0ZXh0byBvdSBjb250ZcO6ZG8gZG8gZG9jdW1lbnRvIGVudHJlZ3VlLgoKU2UgbyBkb2N1bWVudG8gZW50cmVndWUgw6kgYmFzZWFkbyBlbSB0cmFiYWxobyBmaW5hbmNpYWRvIG91IGFwb2lhZG8KcG9yIG91dHJhIGluc3RpdHVpw6fDo28gcXVlIG7Do28gYSBVbml2ZXJzaWRhZGUgRmVkZXJhbCBkbyBDZWFyw6EsIGRlY2xhcmEgcXVlIGN1bXByaXUgcXVhaXNxdWVyIG9icmlnYcOnw7VlcyBleGlnaWRhcyBwZWxvIHJlc3BlY3Rpdm8gY29udHJhdG8gb3UKYWNvcmRvLgoKQSBVbml2ZXJzaWRhZGUgRmVkZXJhbCBkbyBDZWFyw6EgaWRlbnRpZmljYXLDoSBjbGFyYW1lbnRlIG8ocykgc2V1IChzKSBub21lIChzKSBjb21vIG8gKHMpIGF1dG9yIChlcykgb3UgZGV0ZW50b3IgKGVzKSBkb3MgZGlyZWl0b3MgZG8gZG9jdW1lbnRvIGVudHJlZ3VlLCBlIG7Do28gZmFyw6EgcXVhbHF1ZXIgYWx0ZXJhw6fDo28sIHBhcmEgYWzDqW0gZGFzIHBlcm1pdGlkYXMgcG9yIGVzdGEgbGljZW7Dp2EuCg==Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2021-06-16T12:17:15Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Estudo comportamental e neuroquímico em ratos periadolescentes submetidos ao tratamento agudo e subcrônico com efavirenz
dc.title.en.pt_BR.fl_str_mv Behavioral and neurochemical study in periadolescent rats submitted to acute and subchronic treatment with efavirenz
title Estudo comportamental e neuroquímico em ratos periadolescentes submetidos ao tratamento agudo e subcrônico com efavirenz
spellingShingle Estudo comportamental e neuroquímico em ratos periadolescentes submetidos ao tratamento agudo e subcrônico com efavirenz
Cavalcante, Giuliana Ignácio Teixeira
Transtornos Mentais
Sistema Nervoso Central
Efeitos Adversos
title_short Estudo comportamental e neuroquímico em ratos periadolescentes submetidos ao tratamento agudo e subcrônico com efavirenz
title_full Estudo comportamental e neuroquímico em ratos periadolescentes submetidos ao tratamento agudo e subcrônico com efavirenz
title_fullStr Estudo comportamental e neuroquímico em ratos periadolescentes submetidos ao tratamento agudo e subcrônico com efavirenz
title_full_unstemmed Estudo comportamental e neuroquímico em ratos periadolescentes submetidos ao tratamento agudo e subcrônico com efavirenz
title_sort Estudo comportamental e neuroquímico em ratos periadolescentes submetidos ao tratamento agudo e subcrônico com efavirenz
author Cavalcante, Giuliana Ignácio Teixeira
author_facet Cavalcante, Giuliana Ignácio Teixeira
author_role author
dc.contributor.author.fl_str_mv Cavalcante, Giuliana Ignácio Teixeira
dc.contributor.advisor1.fl_str_mv Fonteles, Marta Maria de França
contributor_str_mv Fonteles, Marta Maria de França
dc.subject.por.fl_str_mv Transtornos Mentais
Sistema Nervoso Central
Efeitos Adversos
topic Transtornos Mentais
Sistema Nervoso Central
Efeitos Adversos
description Antiretroviral therapy has revolutionized the treatment of patients infected with human immunodeficiency virus (HIV) because it improved the clinical status of these patients. It is essential that at least one of the drugs used and in this therapy cross the blood-brain barrier, since HIV reaches the central nervous system (CNS), causing damage. Efavirenz is an antiretroviral widely used in HIV and able to cross the blood-brain barrier. However, patients treated with efavirenz are presenting neuropsychiatric disorders such as depression, anxiety, mania, suicidal thoughts, psychosis and hallucinations. Based on these facts, this study aimed to assess whether the behavioral changes anxiety, depression and seizures induced by pilocarpine occur in animals treated with efavirenz with a single dose and for a period of 15 days, using standard models of animal behavior as well as check if the treatment with drug can cause changes in monoamines and amino acids. We used male Wistar rats (35 days, n = 6-8). The animals were treated once with efavirenz in the case of an acute treatment, or 15 days for a subchronic treatment. The treated animals and controls were tested for behavioral elevated plus maze (Plus Maze), Forced Swim, Open Field and seizure induced by pilocarpine. To assess neurochemistry, mice were sacrificed and the brain was removed for the analysis of the following areas of interest: striatum, prefrontal cortex and hippocampus. Were measured monoamines and their metabolites, amino acids and the levels of malondialdehyde (MDA). The results showed that efavirenz caused anxiety and motor abnormalities similar to psychogenic drugs in behavioral tests after acute administration, caused depression in the behavioral test after subchronic treatment, had no effect on the latency of convulsion, altered monoamine metabolites and increased levels MDA. Thus, it is conclude that efavirenz, according to this study, promotes neurochemical changes in the central nervous system, causing neuropsychiatric disorders.
publishDate 2011
dc.date.issued.fl_str_mv 2011
dc.date.accessioned.fl_str_mv 2016-03-22T13:26:43Z
dc.date.available.fl_str_mv 2016-03-22T13:26:43Z
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dc.identifier.citation.fl_str_mv CAVALCANTE, G. I, T. Estudo comportamental e neuroquímico em ratos periadolescentes submetidos ao tratamento agudo e subcrônico com efavirenz. 2011. 121 f. Dissertação (Mestrado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2011.
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/15655
identifier_str_mv CAVALCANTE, G. I, T. Estudo comportamental e neuroquímico em ratos periadolescentes submetidos ao tratamento agudo e subcrônico com efavirenz. 2011. 121 f. Dissertação (Mestrado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2011.
url http://www.repositorio.ufc.br/handle/riufc/15655
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