Estudo dos fatores neuroquímicos associados ao efeito do óleo de peixe sobre parâmetros de recaída em ratos expostos à anfetamina
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações do 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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2021-05-11T12:06:44Z2021-05-11T12:06:44Z2018-08-03http://repositorio.ufsm.br/handle/1/20835Psychostimulant 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.Drogas 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.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade Federal de Santa MariaCentro de Ciências da SaúdePrograma de Pós-Graduação em FarmacologiaUFSMBrasilFarmacologiaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessÁcidos graxos n-3Drogas psicoestimulantesPreferência condicionada de lugarSistema dopaminérgicoEstresse oxidativoN-3 fatty acidsPsychostimulant drugsConditioned place preferenceDopaminergic systemOxidative stressCNPQ::CIENCIAS DA SAUDE::FARMACIAEstudo 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 amphetamineinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisPase, Camila Simonettihttp://lattes.cnpq.br/7729148983836692Bürger, Marilise EscobarXXXXXXXXXXXXXXBortolatto, Cristiani FolhariniXXXXXXXXXXXXXXXOliveira, Mauro Schneider deXXXXXXXXXXXXXXhttp://lattes.cnpq.br/0343009410481289Metz, Vinícia Garzella4003000000056001e652500-9671-4714-8b5f-aeac43df84554a7c7c80-a9c5-4649-b7b5-9650f99dc9bee414b039-9548-413f-9c3a-887aebf8533470df8458-aec0-4576-abdd-9ad2d9aca193c4b00ac8-dd1a-4fc3-86e1-a4275c044653reponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALDIS_PPGFARMACOLOGIA_2018_METZ_VINICIA.pdfDIS_PPGFARMACOLOGIA_2018_METZ_VINICIA.pdfDissertação de Mestradoapplication/pdf1638028http://repositorio.ufsm.br/bitstream/1/20835/1/DIS_PPGFARMACOLOGIA_2018_METZ_VINICIA.pdfed412f2d86a6939cb75cfcfcfbfb7f2fMD51LICENSElicense.txtlicense.txttext/plain; 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dc.title.por.fl_str_mv |
Estudo dos fatores neuroquímicos associados ao efeito do óleo de peixe sobre parâmetros de recaída em ratos expostos à anfetamina |
dc.title.alternative.eng.fl_str_mv |
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.advisor1.fl_str_mv |
Pase, Camila Simonetti |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/7729148983836692 |
dc.contributor.advisor-co1.fl_str_mv |
Bürger, Marilise Escobar |
dc.contributor.advisor-co1Lattes.fl_str_mv |
XXXXXXXXXXXXXX |
dc.contributor.referee1.fl_str_mv |
Bortolatto, Cristiani Folharini |
dc.contributor.referee1Lattes.fl_str_mv |
XXXXXXXXXXXXXXX |
dc.contributor.referee2.fl_str_mv |
Oliveira, Mauro Schneider de |
dc.contributor.referee2Lattes.fl_str_mv |
XXXXXXXXXXXXXX |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/0343009410481289 |
dc.contributor.author.fl_str_mv |
Metz, Vinícia Garzella |
contributor_str_mv |
Pase, Camila Simonetti Bürger, Marilise Escobar Bortolatto, Cristiani Folharini Oliveira, Mauro Schneider de |
dc.subject.por.fl_str_mv |
Ácidos graxos n-3 Drogas psicoestimulantes Preferência condicionada de lugar Sistema dopaminérgico Estresse oxidativo |
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 |
dc.subject.eng.fl_str_mv |
N-3 fatty acids Psychostimulant drugs Conditioned place preference Dopaminergic system Oxidative stress |
dc.subject.cnpq.fl_str_mv |
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.issued.fl_str_mv |
2018-08-03 |
dc.date.accessioned.fl_str_mv |
2021-05-11T12:06:44Z |
dc.date.available.fl_str_mv |
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.relation.cnpq.fl_str_mv |
400300000005 |
dc.relation.confidence.fl_str_mv |
600 |
dc.relation.authority.fl_str_mv |
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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.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Farmacologia |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Farmacologia |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações do 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 |
Biblioteca Digital de Teses e Dissertações do UFSM |
collection |
Biblioteca Digital de Teses e Dissertações do UFSM |
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Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM) |
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atendimento.sib@ufsm.br||tedebc@gmail.com |
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1801485137215488000 |