Estudo dos fatores neuroquímicos associados ao efeito do óleo de peixe sobre parâmetros de recaída em ratos expostos à anfetamina

Detalhes bibliográficos
Autor(a) principal: Metz, Vinícia Garzella
Data de Publicação: 2018
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Manancial - Repositório Digital da UFSM
Texto Completo: http://repositorio.ufsm.br/handle/1/20835
Resumo: Psychostimulant drugs are widely used all over the world. Among them, amphetamines are prominent which beyond to being used clinically have been used as recreational drugs. Currently, its indiscriminate use with recreational purposes raises many concerns due to its high ability to develop tolerance, positive reinforcement, addiction and relapse. The use of amphetamine drugs is also able to trigger oxidative processes and cellular damage, especially in brain areas rich in dopamine. Thus, the search for alternatives that may favor the treatment of drug addiction and reduce relapse rates become essential, considering the damages caused by this disorder to the individual, family and society. The consumption of omega-3 polyunsaturated fatty acids (PUFA n-3) has shown beneficial influences in the prevention and treatment of various diseases affecting the central nervous system (CNS). The aim of this study was to evaluate the influence of fish oil (FO), rich in PUFA- n3, on behavioral parameters of relapse, as well as its effects on biochemical and molecular markers in rats previously conditioned to amphetamine (AMPH) preference. Wistar rats were separated in two experimental groups: AMPH (4 mg / kg, i.p.) and Vehicle (saline solution - 0.9% NaCl, i.p.) and submitted to the conditioned place preference (CPP) protocol for 14 days. After the CPP test, half of each experimental group was treated orally with FO (3g / kg, p.o.) or water (Control group) for 14 days by gavage. After the treatment/extinction period to the AMPH, the animals that were previously conditioned with the drug were re-exposed to the AMPH/Vehicle for another 3 days and in the sequence the CPP test was again performed. One day after the end of the behavioral evaluations, the animals were euthanized and the prefrontal cortex (PFC) was collected for biochemical and molecular analysis. The results show that treatment with FO reduced the relapse behavior induced by re-conditioning with AMPH. FO, rich in PUFA n-3, increased the incorporation of DHA into the neural membranes of the PFC. In addition, FO treatment was able to protect the CNS against the toxic effects of AMPH by modulating the dopaminergic cascade markers (DAT, TH, VMAT2, D1R and D2R). Furthermore, FO reduced oxidative damage induced by AMPH in the same brain region. In summary, this study provides evidence that an experimental treatment with PUFA n-3 is capable of altering the neurotransmission of the dopaminergic system, reversing the neurotoxic effects caused by the use of AMPH. Thus, this nutraceutical may be an alternative strategy to assist in the treatment of an important public health problem.
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spelling Estudo dos fatores neuroquímicos associados ao efeito do óleo de peixe sobre parâmetros de recaída em ratos expostos à anfetaminaStudy of neurochemical factors associated to the effect of fish oil on relapse parameters in rats exposed to amphetamineÁcidos graxos n-3Drogas psicoestimulantesPreferência condicionada de lugarSistema dopaminérgicoEstresse oxidativoN-3 fatty acidsPsychostimulant drugsConditioned place preferenceDopaminergic systemOxidative stressCNPQ::CIENCIAS DA SAUDE::FARMACIAPsychostimulant drugs are widely used all over the world. Among them, amphetamines are prominent which beyond to being used clinically have been used as recreational drugs. Currently, its indiscriminate use with recreational purposes raises many concerns due to its high ability to develop tolerance, positive reinforcement, addiction and relapse. The use of amphetamine drugs is also able to trigger oxidative processes and cellular damage, especially in brain areas rich in dopamine. Thus, the search for alternatives that may favor the treatment of drug addiction and reduce relapse rates become essential, considering the damages caused by this disorder to the individual, family and society. The consumption of omega-3 polyunsaturated fatty acids (PUFA n-3) has shown beneficial influences in the prevention and treatment of various diseases affecting the central nervous system (CNS). The aim of this study was to evaluate the influence of fish oil (FO), rich in PUFA- n3, on behavioral parameters of relapse, as well as its effects on biochemical and molecular markers in rats previously conditioned to amphetamine (AMPH) preference. Wistar rats were separated in two experimental groups: AMPH (4 mg / kg, i.p.) and Vehicle (saline solution - 0.9% NaCl, i.p.) and submitted to the conditioned place preference (CPP) protocol for 14 days. After the CPP test, half of each experimental group was treated orally with FO (3g / kg, p.o.) or water (Control group) for 14 days by gavage. After the treatment/extinction period to the AMPH, the animals that were previously conditioned with the drug were re-exposed to the AMPH/Vehicle for another 3 days and in the sequence the CPP test was again performed. One day after the end of the behavioral evaluations, the animals were euthanized and the prefrontal cortex (PFC) was collected for biochemical and molecular analysis. The results show that treatment with FO reduced the relapse behavior induced by re-conditioning with AMPH. FO, rich in PUFA n-3, increased the incorporation of DHA into the neural membranes of the PFC. In addition, FO treatment was able to protect the CNS against the toxic effects of AMPH by modulating the dopaminergic cascade markers (DAT, TH, VMAT2, D1R and D2R). Furthermore, FO reduced oxidative damage induced by AMPH in the same brain region. In summary, this study provides evidence that an experimental treatment with PUFA n-3 is capable of altering the neurotransmission of the dopaminergic system, reversing the neurotoxic effects caused by the use of AMPH. Thus, this nutraceutical may be an alternative strategy to assist in the treatment of an important public health problem.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESDrogas psicoestimulantes são amplamente utilizadas em todo o mundo. Dentre elas, destacam-se as anfetaminas, as quais além de serem empregadas clinicamente, têm sido utilizadas como drogas recreativas. Atualmente, seu uso indiscriminado com fins recreacionais gera inúmeras preocupações devido a sua alta capacidade de desenvolver tolerância, reforço positivo, dependência e recaídas. O uso de drogas anfetamínicas também é capaz de desencadear processos oxidativos e danos celulares, principalmente em áreas cerebrais ricas em dopamina. Deste modo, a busca por alternativas que possam favorecer o tratamento de drogadição e reduzir os índices de recaída tornam-se imprescindíveis, considerando os prejuízos ocasionados por esse transtorno ao indivíduo, à família e à sociedade. O consumo de ácidos graxos poli-insaturados ômega-3 (AGPI n-3) têm mostrado influências benéficas na prevenção e tratamento de diversas doenças que afetam o sistema nervoso central. Diante disso, o objetivo deste estudo foi avaliar a influência do óleo de peixe (OP), rico em AGPI-3, sobre parâmetros comportamentais de recaída, bem como seus efeitos sobre marcadores bioquímicos e moleculares em ratos previamente condicionados à preferência por anfetamina (ANF). Ratos Wistar foram separados em dois grupos experimentais: ANF (4 mg/kg, i.p.) e Veículo (solução salina - 0,9% NaCl, i.p.) e submetidos ao protocolo de preferência condicionada de lugar (PCL) por 14 dias. Após o teste de PCL, a metade de cada grupo experimental foi tratada oralmente com OP (3g/kg, p.o.) ou água (grupo Controle) durante 14 dias por sonda esofágica. Após o período de tratamento/extinção à ANF, os animais que foram previamente condicionados com o fármaco foram re-expostos à ANF/Veículo por mais 3 dias e na sequência foi novamente realizado o teste de PCL. Um dia após o final das avaliações comportamentais, os animais foram eutanasiados e o córtex pré-frontal (CPF) foi coletado para análises bioquímicas e moleculares. Os resultados encontrados mostram que o tratamento com OP reduziu o comportamento de recaída induzido pelo re-condicionamento com ANF. O OP, rico em AGPI n-3, aumentou a incorporação de DHA nas membranas neuronais do CPF. Além disso, o tratamento com OP foi capaz de proteger o SNC contra os efeitos tóxicos da ANF, modulando os marcadores da cascata dopaminérgica (DAT, TH, VMAT2, D1R e D2R). Ainda, o FO reduziu os danos oxidativos induzidos pela ANF na mesma região cerebral. Em resumo, esse estudo fornece evidências de que um tratamento experimental com AGPI n-3 é capaz de alterar a neurotransmissão do sistema dopaminérgico, revertendo os efeitos neurotóxicos provocados pelo uso de ANF. Dessa maneira, este nutracêutico pode ser uma estratégia alternativa para auxiliar no tratamento de um importante problema de saúde pública.Universidade Federal de Santa MariaBrasilFarmacologiaUFSMPrograma de Pós-Graduação em FarmacologiaCentro de Ciências da SaúdePase, Camila Simonettihttp://lattes.cnpq.br/7729148983836692Bürger, Marilise EscobarXXXXXXXXXXXXXXBortolatto, Cristiani FolhariniXXXXXXXXXXXXXXXOliveira, Mauro Schneider deXXXXXXXXXXXXXXMetz, Vinícia Garzella2021-05-11T12:06:44Z2021-05-11T12:06:44Z2018-08-03info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/20835porAttribution-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:UFSM2022-08-12T14:30:58Zoai:repositorio.ufsm.br:1/20835Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2022-08-12T14:30:58Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false
dc.title.none.fl_str_mv Estudo dos fatores neuroquímicos associados ao efeito do óleo de peixe sobre parâmetros de recaída em ratos expostos à anfetamina
Study of neurochemical factors associated to the effect of fish oil on relapse parameters in rats exposed to amphetamine
title Estudo dos fatores neuroquímicos associados ao efeito do óleo de peixe sobre parâmetros de recaída em ratos expostos à anfetamina
spellingShingle Estudo dos fatores neuroquímicos associados ao efeito do óleo de peixe sobre parâmetros de recaída em ratos expostos à anfetamina
Metz, Vinícia Garzella
Ácidos graxos n-3
Drogas psicoestimulantes
Preferência condicionada de lugar
Sistema dopaminérgico
Estresse oxidativo
N-3 fatty acids
Psychostimulant drugs
Conditioned place preference
Dopaminergic system
Oxidative stress
CNPQ::CIENCIAS DA SAUDE::FARMACIA
title_short Estudo dos fatores neuroquímicos associados ao efeito do óleo de peixe sobre parâmetros de recaída em ratos expostos à anfetamina
title_full Estudo dos fatores neuroquímicos associados ao efeito do óleo de peixe sobre parâmetros de recaída em ratos expostos à anfetamina
title_fullStr Estudo dos fatores neuroquímicos associados ao efeito do óleo de peixe sobre parâmetros de recaída em ratos expostos à anfetamina
title_full_unstemmed Estudo dos fatores neuroquímicos associados ao efeito do óleo de peixe sobre parâmetros de recaída em ratos expostos à anfetamina
title_sort Estudo dos fatores neuroquímicos associados ao efeito do óleo de peixe sobre parâmetros de recaída em ratos expostos à anfetamina
author Metz, Vinícia Garzella
author_facet Metz, Vinícia Garzella
author_role author
dc.contributor.none.fl_str_mv Pase, Camila Simonetti
http://lattes.cnpq.br/7729148983836692
Bürger, Marilise Escobar
XXXXXXXXXXXXXX
Bortolatto, Cristiani Folharini
XXXXXXXXXXXXXXX
Oliveira, Mauro Schneider de
XXXXXXXXXXXXXX
dc.contributor.author.fl_str_mv Metz, Vinícia Garzella
dc.subject.por.fl_str_mv Ácidos graxos n-3
Drogas psicoestimulantes
Preferência condicionada de lugar
Sistema dopaminérgico
Estresse oxidativo
N-3 fatty acids
Psychostimulant drugs
Conditioned place preference
Dopaminergic system
Oxidative stress
CNPQ::CIENCIAS DA SAUDE::FARMACIA
topic Ácidos graxos n-3
Drogas psicoestimulantes
Preferência condicionada de lugar
Sistema dopaminérgico
Estresse oxidativo
N-3 fatty acids
Psychostimulant drugs
Conditioned place preference
Dopaminergic system
Oxidative stress
CNPQ::CIENCIAS DA SAUDE::FARMACIA
description Psychostimulant drugs are widely used all over the world. Among them, amphetamines are prominent which beyond to being used clinically have been used as recreational drugs. Currently, its indiscriminate use with recreational purposes raises many concerns due to its high ability to develop tolerance, positive reinforcement, addiction and relapse. The use of amphetamine drugs is also able to trigger oxidative processes and cellular damage, especially in brain areas rich in dopamine. Thus, the search for alternatives that may favor the treatment of drug addiction and reduce relapse rates become essential, considering the damages caused by this disorder to the individual, family and society. The consumption of omega-3 polyunsaturated fatty acids (PUFA n-3) has shown beneficial influences in the prevention and treatment of various diseases affecting the central nervous system (CNS). The aim of this study was to evaluate the influence of fish oil (FO), rich in PUFA- n3, on behavioral parameters of relapse, as well as its effects on biochemical and molecular markers in rats previously conditioned to amphetamine (AMPH) preference. Wistar rats were separated in two experimental groups: AMPH (4 mg / kg, i.p.) and Vehicle (saline solution - 0.9% NaCl, i.p.) and submitted to the conditioned place preference (CPP) protocol for 14 days. After the CPP test, half of each experimental group was treated orally with FO (3g / kg, p.o.) or water (Control group) for 14 days by gavage. After the treatment/extinction period to the AMPH, the animals that were previously conditioned with the drug were re-exposed to the AMPH/Vehicle for another 3 days and in the sequence the CPP test was again performed. One day after the end of the behavioral evaluations, the animals were euthanized and the prefrontal cortex (PFC) was collected for biochemical and molecular analysis. The results show that treatment with FO reduced the relapse behavior induced by re-conditioning with AMPH. FO, rich in PUFA n-3, increased the incorporation of DHA into the neural membranes of the PFC. In addition, FO treatment was able to protect the CNS against the toxic effects of AMPH by modulating the dopaminergic cascade markers (DAT, TH, VMAT2, D1R and D2R). Furthermore, FO reduced oxidative damage induced by AMPH in the same brain region. In summary, this study provides evidence that an experimental treatment with PUFA n-3 is capable of altering the neurotransmission of the dopaminergic system, reversing the neurotoxic effects caused by the use of AMPH. Thus, this nutraceutical may be an alternative strategy to assist in the treatment of an important public health problem.
publishDate 2018
dc.date.none.fl_str_mv 2018-08-03
2021-05-11T12:06:44Z
2021-05-11T12:06:44Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://repositorio.ufsm.br/handle/1/20835
url http://repositorio.ufsm.br/handle/1/20835
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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