Efeitos neuroendócrinos e comportamentais do aripiprazol em zebrafish

Detalhes bibliográficos
Autor(a) principal: Barcellos, Heloísa Helena de Alcântara
Data de Publicação: 2019
Tipo de documento: Tese
Idioma: por
Título da fonte: Manancial - Repositório Digital da UFSM
Texto Completo: http://repositorio.ufsm.br/handle/1/15911
Resumo: The aripiprazole (APPZ) is a second-generation atypical antipsychotic, which has been increasingly used in the treatment of psychoses, such as schizophrenia, autism, bipolar affective disorder, among others. The increasing use of this drug occurs because it causes less extrapyramidal effects compared to typical antipsychotics. Associated with the increase in prescriptions and, consequently, in the consumption of this drug, there is, consequently, a growing risk of environmental contamination by its residues, either in active form or in the form of metabolites. These residues in the environment can affect non-target organisms such as fish, interfering negatively in their homeostasis and in their physiological defense mechanisms. Several studies have demonstrated the problematic of the contamination of aquatic environments and the impact on the fauna of these ecosystems by several psychotropic drugs. In this context, the aim of the present study was to verify if aripiprazole changes the endocrine and behavioral responses to stress in adult zebrafish. We have shown, based on the results described in the two articles presented, that APPZ residues in water produce effects on both the hypothalamic-pituitary-interrenal (HHI) axis and in the behavior of adult zebrafish. In the first article, we show that the fish previously exposed to APPZ, when subjected to the acute stressor, presented a blunted cortisol response to stress. Regarding to the effect of APPZ on zebrafish behavior, we observed that some of the tested concentrations reversed the behavioral response to stress in both the social preference, the anxiety-like behavior and the perception of a stimulus fish, whether predator or not predator. Thus, we conclude that acute exposure to APPZ is capable of blunting the neuroendocrine axis of stress in adult zebrafish, as well as altering exploratory and social behavior and reaction to a predatory threat. In an ecological context, the sum of these endocrine and behavioral effects caused by APPZ may expose fish to a greater risk of predation and, consequently, increase the risk of broken of ecological balance between species, and consequently impact the aquatic ecosystem.
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spelling Efeitos neuroendócrinos e comportamentais do aripiprazol em zebrafishNeuroendocrine and behavioral effects of aripiprazole in zebrafishDanio rerioCortisolContaminação ambientalComportamento exploratórioComportamento socialReação anti-predatóriaEnvironmental contaminationExploratory behaviorSocial behaviorAnti-predatory reactionCNPQ::CIENCIAS DA SAUDE::FARMACIAThe aripiprazole (APPZ) is a second-generation atypical antipsychotic, which has been increasingly used in the treatment of psychoses, such as schizophrenia, autism, bipolar affective disorder, among others. The increasing use of this drug occurs because it causes less extrapyramidal effects compared to typical antipsychotics. Associated with the increase in prescriptions and, consequently, in the consumption of this drug, there is, consequently, a growing risk of environmental contamination by its residues, either in active form or in the form of metabolites. These residues in the environment can affect non-target organisms such as fish, interfering negatively in their homeostasis and in their physiological defense mechanisms. Several studies have demonstrated the problematic of the contamination of aquatic environments and the impact on the fauna of these ecosystems by several psychotropic drugs. In this context, the aim of the present study was to verify if aripiprazole changes the endocrine and behavioral responses to stress in adult zebrafish. We have shown, based on the results described in the two articles presented, that APPZ residues in water produce effects on both the hypothalamic-pituitary-interrenal (HHI) axis and in the behavior of adult zebrafish. In the first article, we show that the fish previously exposed to APPZ, when subjected to the acute stressor, presented a blunted cortisol response to stress. Regarding to the effect of APPZ on zebrafish behavior, we observed that some of the tested concentrations reversed the behavioral response to stress in both the social preference, the anxiety-like behavior and the perception of a stimulus fish, whether predator or not predator. Thus, we conclude that acute exposure to APPZ is capable of blunting the neuroendocrine axis of stress in adult zebrafish, as well as altering exploratory and social behavior and reaction to a predatory threat. In an ecological context, the sum of these endocrine and behavioral effects caused by APPZ may expose fish to a greater risk of predation and, consequently, increase the risk of broken of ecological balance between species, and consequently impact the aquatic ecosystem.O aripiprazol (APPZ) é um antipsicótico atípico de segunda geração, que vem sendo cada vez mais utilizado no tratamento de psicoses, tais como esquizofrenia, autismo, transtorno afetivo bipolar, entre outros. A crescente utilização deste fármaco se dá porque ele provoca menos efeitos extrapiramidais em relação aos antipsicóticos típicos. Associado ao aumento nas prescrições e, consequentemente, no consumo deste medicamento, existe o risco, também crescente, de contaminação ambiental por seus resíduos, seja em forma ativa ou em forma de metabólitos. Estes resíduos no ambiente podem afetar organismos não alvo como os peixes, interferindo de forma negativa na sua homeostase e em seus mecanismos fisiológicos de defesa. Vários estudos têm demostrado a problemática da contaminação de ambientes aquáticos e o impacto sobre a fauna desses ecossistemas por diversos psicofármacos. Nesse contexto, o objetivo geral do presente trabalho foi o de verificar se o APPZ altera as respostas endócrinas e comportamentais ao estresse em zebrafish adultos. Nós mostramos, com base nos resultados descritos nos dois artigos produzidos, que os resíduos de APPZ na água produzem efeitos tanto no eixo hipotálamo-hipófise-interrenal (HHI) quanto no comportamento do zebrafish adulto. No primeiro artigo, podemos evidenciar que os peixes expostos previamente ao APPZ, quando submetidos ao estímulo estressor agudo, tiveram um claro embotamento da resposta de cortisol ao estresse. Em relação ao efeito do APPZ sobre o comportamento do zebrafish, observamos que algumas concentrações reverteram a resposta comportamental ao estresse tanto no aspecto de preferência social, quanto no comportamento do tipo-ansiedade e na percepção de um peixe estímulo, seja predador ou não predador. Assim, concluímos que a exposição aguda ao APPZ é capaz de causar o embotamento do eixo neuroendócrino de estresse em zebrafish adultos, bem como alterar o comportamento exploratório e social e a reação frente a uma ameaça predatória. Num contexto ecológico, o somatório desses efeitos endócrinos e comportamentais causados pelo APPZ pode expor os peixes a um maior risco de predação e, consequentemente pôr em risco o equilíbrio ecológico entre as espécies que compõem o ecossistema aquático.Universidade Federal de Santa MariaBrasilFarmacologiaUFSMPrograma de Pós-Graduação em FarmacologiaCentro de Ciências da SaúdeBaldisserotto, Bernardohttp://lattes.cnpq.br/1036046601275319Bonan, Carla Denisehttp://lattes.cnpq.br/8058052532279136Cunha, Mauro Alves dahttp://lattes.cnpq.br/9745413680917763Oliveira, Diogo Losch dehttp://lattes.cnpq.br/3056695127432911Kreutz, Luiz Carloshttp://lattes.cnpq.br/6207090944092820Barcellos, Heloísa Helena de Alcântara2019-03-14T21:41:54Z2019-03-14T21:41:54Z2019-01-17info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/15911porAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2019-03-15T06:02:23Zoai:repositorio.ufsm.br:1/15911Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2019-03-15T06:02:23Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false
dc.title.none.fl_str_mv Efeitos neuroendócrinos e comportamentais do aripiprazol em zebrafish
Neuroendocrine and behavioral effects of aripiprazole in zebrafish
title Efeitos neuroendócrinos e comportamentais do aripiprazol em zebrafish
spellingShingle Efeitos neuroendócrinos e comportamentais do aripiprazol em zebrafish
Barcellos, Heloísa Helena de Alcântara
Danio rerio
Cortisol
Contaminação ambiental
Comportamento exploratório
Comportamento social
Reação anti-predatória
Environmental contamination
Exploratory behavior
Social behavior
Anti-predatory reaction
CNPQ::CIENCIAS DA SAUDE::FARMACIA
title_short Efeitos neuroendócrinos e comportamentais do aripiprazol em zebrafish
title_full Efeitos neuroendócrinos e comportamentais do aripiprazol em zebrafish
title_fullStr Efeitos neuroendócrinos e comportamentais do aripiprazol em zebrafish
title_full_unstemmed Efeitos neuroendócrinos e comportamentais do aripiprazol em zebrafish
title_sort Efeitos neuroendócrinos e comportamentais do aripiprazol em zebrafish
author Barcellos, Heloísa Helena de Alcântara
author_facet Barcellos, Heloísa Helena de Alcântara
author_role author
dc.contributor.none.fl_str_mv Baldisserotto, Bernardo
http://lattes.cnpq.br/1036046601275319
Bonan, Carla Denise
http://lattes.cnpq.br/8058052532279136
Cunha, Mauro Alves da
http://lattes.cnpq.br/9745413680917763
Oliveira, Diogo Losch de
http://lattes.cnpq.br/3056695127432911
Kreutz, Luiz Carlos
http://lattes.cnpq.br/6207090944092820
dc.contributor.author.fl_str_mv Barcellos, Heloísa Helena de Alcântara
dc.subject.por.fl_str_mv Danio rerio
Cortisol
Contaminação ambiental
Comportamento exploratório
Comportamento social
Reação anti-predatória
Environmental contamination
Exploratory behavior
Social behavior
Anti-predatory reaction
CNPQ::CIENCIAS DA SAUDE::FARMACIA
topic Danio rerio
Cortisol
Contaminação ambiental
Comportamento exploratório
Comportamento social
Reação anti-predatória
Environmental contamination
Exploratory behavior
Social behavior
Anti-predatory reaction
CNPQ::CIENCIAS DA SAUDE::FARMACIA
description The aripiprazole (APPZ) is a second-generation atypical antipsychotic, which has been increasingly used in the treatment of psychoses, such as schizophrenia, autism, bipolar affective disorder, among others. The increasing use of this drug occurs because it causes less extrapyramidal effects compared to typical antipsychotics. Associated with the increase in prescriptions and, consequently, in the consumption of this drug, there is, consequently, a growing risk of environmental contamination by its residues, either in active form or in the form of metabolites. These residues in the environment can affect non-target organisms such as fish, interfering negatively in their homeostasis and in their physiological defense mechanisms. Several studies have demonstrated the problematic of the contamination of aquatic environments and the impact on the fauna of these ecosystems by several psychotropic drugs. In this context, the aim of the present study was to verify if aripiprazole changes the endocrine and behavioral responses to stress in adult zebrafish. We have shown, based on the results described in the two articles presented, that APPZ residues in water produce effects on both the hypothalamic-pituitary-interrenal (HHI) axis and in the behavior of adult zebrafish. In the first article, we show that the fish previously exposed to APPZ, when subjected to the acute stressor, presented a blunted cortisol response to stress. Regarding to the effect of APPZ on zebrafish behavior, we observed that some of the tested concentrations reversed the behavioral response to stress in both the social preference, the anxiety-like behavior and the perception of a stimulus fish, whether predator or not predator. Thus, we conclude that acute exposure to APPZ is capable of blunting the neuroendocrine axis of stress in adult zebrafish, as well as altering exploratory and social behavior and reaction to a predatory threat. In an ecological context, the sum of these endocrine and behavioral effects caused by APPZ may expose fish to a greater risk of predation and, consequently, increase the risk of broken of ecological balance between species, and consequently impact the aquatic ecosystem.
publishDate 2019
dc.date.none.fl_str_mv 2019-03-14T21:41:54Z
2019-03-14T21:41:54Z
2019-01-17
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.uri.fl_str_mv http://repositorio.ufsm.br/handle/1/15911
url http://repositorio.ufsm.br/handle/1/15911
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Santa Maria
Brasil
Farmacologia
UFSM
Programa de Pós-Graduação em Farmacologia
Centro de Ciências da Saúde
publisher.none.fl_str_mv Universidade Federal de Santa Maria
Brasil
Farmacologia
UFSM
Programa de Pós-Graduação em Farmacologia
Centro de Ciências da Saúde
dc.source.none.fl_str_mv reponame:Manancial - Repositório Digital da UFSM
instname:Universidade Federal de Santa Maria (UFSM)
instacron:UFSM
instname_str Universidade Federal de Santa Maria (UFSM)
instacron_str UFSM
institution UFSM
reponame_str Manancial - Repositório Digital da UFSM
collection Manancial - Repositório Digital da UFSM
repository.name.fl_str_mv Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)
repository.mail.fl_str_mv atendimento.sib@ufsm.br||tedebc@gmail.com
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