Influência dos ácidos graxos da dieta sobre parâmetros de adicção à anfetamina em ratos: aspectos comportamentais, bioquímicos e moleculares

Detalhes bibliográficos
Ano de defesa: 2015
Autor(a) principal: Kuhn, Fábio Teixeira lattes
Orientador(a): Burger, Marilise Escobar lattes
Banca de defesa: Furian, Ana Flávia lattes, Marin, Marcelo Tadeu lattes, Oliveira, Mauro Schneider lattes, Oliveira, Sara Marchesan de lattes
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal de Santa Maria
Centro de Ciências da Saúde
Programa de Pós-Graduação: Programa de Pós-Graduação em Farmacologia
Departamento: Farmacologia
País: Brasil
Palavras-chave em Português:
Palavras-chave em Inglês:
Área do conhecimento CNPq:
Link de acesso: http://repositorio.ufsm.br/handle/1/17570
Resumo: Polyunsaturated fatty acids (PUFA) are constituents of neuronal membrane phospholipids which play key roles in the development and functioning of the brain. The last decades have been accompanied by changes in dietary habits, especially in Western countries through the industrialization of foods, which contributed to the increased consumption of trans fatty acids (TFA) and omega-6 fatty acid (FA n-6) over AG omega-3 (n-3). Recent studies of our group have shown that such dietary changes can alter the composition of neuronal membrane phospholipids, altering the dopaminergic system, which may facilitate the preference for psychostimulant addictive drugs. This study was conducted through two experimental protocols: 1) adult Wistar rats were divided into four experimental groups were daily supplemented with soybean oil (SO rich in PUFA n-6), fish oil (FO rich in PUFAs n-3) or hydrogenated vegetable fat (HVF, rich in TFAs) and control group (supplemented with water), from pre-conception period until weaning of the 2nd generation, whose offspring remained the same supplements until 40 post-natal day (PND). Male rats born from the 2nd generation were conditioned in protocol preference with amphetamine (AMPH), and subsequently under behavioral observation rather than for drug development of anxiety, assessment of lipid profile of brain tissue, as well as parameters of stress oxidative the same brain areas; 2) adult Wistar rats, divided into three experimental groups were supplemented daily with a mixture of SO and FO which was generating an ideal ratio of PUFA n-6/n-3 (2:1) or HVF and control group (supplemented with water), since the pre-conceptional period until weaning of 1st generation, whose male pups were kept under the same progenitor supplements until 50 post-natal day when they were submitted to a protocol of self-administration of AMPH, followed by behavioral assessments, analysis and molecular incorporation of FA profile in different brain areas. Animals supplemented by 2nd generation HVF showed incorporation of TFA in whole brain, and increased preference for AMPH, indicating the involvement of changes in dopaminergic circuitry. Animals supplemented with HVF 1st generation had a higher frequency of self-administration of AMPH, indicating greater degree of addiction by psychostimulant. The animals supplemented with HVF in both experimental protocols showed a higher degree of anxiety, the two generations of rats showed increased oxidative status, accompanied by molecular damage in dopaminergic brain areas. The results show that chronic consumption of trans fats at the expense of polyunsaturated fatty acids especially the n-3 series, may modify the constitution of lipid membranes and affect neuronal plasticity, modifying dopaminergic neurotransmission, which is strongly associated with the development of addiction by psychostimulant drugs, and anxiety which is one of the symptoms of AMPHaddiction.
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spelling 2019-07-26T19:30:16Z2019-07-26T19:30:16Z2015-07-16http://repositorio.ufsm.br/handle/1/17570Polyunsaturated fatty acids (PUFA) are constituents of neuronal membrane phospholipids which play key roles in the development and functioning of the brain. The last decades have been accompanied by changes in dietary habits, especially in Western countries through the industrialization of foods, which contributed to the increased consumption of trans fatty acids (TFA) and omega-6 fatty acid (FA n-6) over AG omega-3 (n-3). Recent studies of our group have shown that such dietary changes can alter the composition of neuronal membrane phospholipids, altering the dopaminergic system, which may facilitate the preference for psychostimulant addictive drugs. This study was conducted through two experimental protocols: 1) adult Wistar rats were divided into four experimental groups were daily supplemented with soybean oil (SO rich in PUFA n-6), fish oil (FO rich in PUFAs n-3) or hydrogenated vegetable fat (HVF, rich in TFAs) and control group (supplemented with water), from pre-conception period until weaning of the 2nd generation, whose offspring remained the same supplements until 40 post-natal day (PND). Male rats born from the 2nd generation were conditioned in protocol preference with amphetamine (AMPH), and subsequently under behavioral observation rather than for drug development of anxiety, assessment of lipid profile of brain tissue, as well as parameters of stress oxidative the same brain areas; 2) adult Wistar rats, divided into three experimental groups were supplemented daily with a mixture of SO and FO which was generating an ideal ratio of PUFA n-6/n-3 (2:1) or HVF and control group (supplemented with water), since the pre-conceptional period until weaning of 1st generation, whose male pups were kept under the same progenitor supplements until 50 post-natal day when they were submitted to a protocol of self-administration of AMPH, followed by behavioral assessments, analysis and molecular incorporation of FA profile in different brain areas. Animals supplemented by 2nd generation HVF showed incorporation of TFA in whole brain, and increased preference for AMPH, indicating the involvement of changes in dopaminergic circuitry. Animals supplemented with HVF 1st generation had a higher frequency of self-administration of AMPH, indicating greater degree of addiction by psychostimulant. The animals supplemented with HVF in both experimental protocols showed a higher degree of anxiety, the two generations of rats showed increased oxidative status, accompanied by molecular damage in dopaminergic brain areas. The results show that chronic consumption of trans fats at the expense of polyunsaturated fatty acids especially the n-3 series, may modify the constitution of lipid membranes and affect neuronal plasticity, modifying dopaminergic neurotransmission, which is strongly associated with the development of addiction by psychostimulant drugs, and anxiety which is one of the symptoms of AMPHaddiction.Ácidos graxos poliinsaturados (AGPI) são constituintes das membranas fosfolipídicas neuronais onde exercem funções fundamentais para o desenvolvimento e funcionamento do cérebro. As últimas décadas foram acompanhadas de mudanças nos hábitos alimentares, especialmente em países ocidentais, devido à industrialização dos alimentos, o que contribuiu para o consumo aumentado de ácidos graxos trans (AGT) e ácidos graxos ômega-6 (AG n-6) em detrimento de AG ômega-3 (n-3). Recentes estudos do nosso grupo tem mostrado que tais mudanças alimentares podem modificar a composição das membranas fosfolipídicas neurais, modificando o sistema dopaminérgico, o que pode facilitar a preferência por drogas aditivas psicoestimulantes. O presente estudo foi conduzido através de dois protocolos experimentais: 1) Ratas Wistar adultas, divididas em quatro grupos experimentais, foram suplementadas diariamente com óleo de soja (OS, rico em AGPI n-6), óleo de peixe (OP, rico em AGPI n-3) ou gordura vegetal hidrogenada (GVH, rica em AGT) e grupo controle (suplementados com água), desde o período pré-concepcional até o desmame da 2ª geração, cujos filhotes permaneceram nas mesmas suplementações até os 40 dias pós-natal. Ratos machos nascidos a partir da 2ª geração foram condicionados ao protocolo de preferência com anfetamina (ANF), e posteriormente submetidos à protocolos de observação comportamental de preferência à droga, desenvolvimento de ansiedade, avaliação do perfil lipídico dos tecidos cerebrais, bem como parâmetros de estresse oxidativo nas mesmas áreas cerebrais; 2) Ratas Wistar adultas, designadas em três grupos experimentais, foram diariamente suplementadas com uma mistura de OS e OP gerando uma razão ideal de AGPI n-6:n-3 (2:1) ou GVH, e grupo controle (suplementados com água), desde o período pré-concepcional até o desmame da 1ª geração, cujos filhotes machos foram mantidos sob as mesmas suplementações das progenitoras até os 50 dias pós-natal, quando foram submetidos à um protocolo de autoadministração de ANF, seguido de avaliações comportamentais, análises moleculares e perfil de incorporação de AG em diferentes áreas cerebrais. Animais de 2ª geração suplementados com GVH apresentaram incorporação de AGT em regiões cerebrais relacionadas à adicção, e maior preferência por ANF, indicando o envolvimento de alterações no circuito dopaminérgico. Animais de 1ª geração suplementados com GVH apresentaram maior frequência de autoadministração de ANF, indicando maior grau de adicção pelo psicoestimulante. Além dos animais suplementados com GVH de ambos protocolos experimentais terem apresentado maior grau de ansiedade, as duas gerações de ratos apresentaram maior estatus oxidativo, acompanhados de modificações moleculares em áreas dopaminérgicas cerebrais. Os resultados mostram que o consumo crônico de gorduras trans, em detrimento de ácidos graxos poliinsaturados principalmente da série n-3, pode modificar a constituição lipídica das membranas neuronais e afetar sua plasticidade, modificando a neurotransmissão dopaminérgica, a qual está fortemente associada ao desenvolvimento de adicção por drogas psicoestimulantes, além de ansiedade que é um dos sintomas da dependência pela ANF.Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, FAPERGS, Brasil.porUniversidade 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 transAnfetaminasÔmega-3Drogas de abusoAdicçãoTrans fatty acidsAmphetamineOmega-3AddictionCNPQ::CIENCIAS DA SAUDE::FARMACIAInfluência dos ácidos graxos da dieta sobre parâmetros de adicção à anfetamina em ratos: aspectos comportamentais, bioquímicos e molecularesInfluence of different dietary fatty acids on amphetamine addiction parameters in rats: behavior, biochemical and molecularinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisBurger, Marilise Escobarhttp://lattes.cnpq.br/9128090974948413Furian, Ana Fláviahttp://lattes.cnpq.br/0865191340133424Marin, Marcelo Tadeuhttp://lattes.cnpq.br/7920438802539727Oliveira, Mauro Schneiderhttp://lattes.cnpq.br/7132934163734175Oliveira, Sara Marchesan dehttp://lattes.cnpq.br/6574555059806902http://lattes.cnpq.br/6420900984677569Kuhn, Fábio Teixeira400300000005600cea6b067-f9a7-4654-8ec5-65f1c465c1a8b4fd1ef0-281a-4204-ad97-6abbb6f22485e6900342-97ef-4bb8-a11a-5b60f732af6e26fdcb03-2a73-4385-b8f2-46ab26387eeadf67a9a8-bb2b-4fe4-b1ab-0baffdb61ead4075277b-8b36-46ac-b25d-abf48b5aa548reponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv Influência dos ácidos graxos da dieta sobre parâmetros de adicção à anfetamina em ratos: aspectos comportamentais, bioquímicos e moleculares
dc.title.alternative.eng.fl_str_mv Influence of different dietary fatty acids on amphetamine addiction parameters in rats: behavior, biochemical and molecular
title Influência dos ácidos graxos da dieta sobre parâmetros de adicção à anfetamina em ratos: aspectos comportamentais, bioquímicos e moleculares
spellingShingle Influência dos ácidos graxos da dieta sobre parâmetros de adicção à anfetamina em ratos: aspectos comportamentais, bioquímicos e moleculares
Kuhn, Fábio Teixeira
Ácidos graxos trans
Anfetaminas
Ômega-3
Drogas de abuso
Adicção
Trans fatty acids
Amphetamine
Omega-3
Addiction
CNPQ::CIENCIAS DA SAUDE::FARMACIA
title_short Influência dos ácidos graxos da dieta sobre parâmetros de adicção à anfetamina em ratos: aspectos comportamentais, bioquímicos e moleculares
title_full Influência dos ácidos graxos da dieta sobre parâmetros de adicção à anfetamina em ratos: aspectos comportamentais, bioquímicos e moleculares
title_fullStr Influência dos ácidos graxos da dieta sobre parâmetros de adicção à anfetamina em ratos: aspectos comportamentais, bioquímicos e moleculares
title_full_unstemmed Influência dos ácidos graxos da dieta sobre parâmetros de adicção à anfetamina em ratos: aspectos comportamentais, bioquímicos e moleculares
title_sort Influência dos ácidos graxos da dieta sobre parâmetros de adicção à anfetamina em ratos: aspectos comportamentais, bioquímicos e moleculares
author Kuhn, Fábio Teixeira
author_facet Kuhn, Fábio Teixeira
author_role author
dc.contributor.advisor1.fl_str_mv Burger, Marilise Escobar
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/9128090974948413
dc.contributor.referee1.fl_str_mv Furian, Ana Flávia
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/0865191340133424
dc.contributor.referee2.fl_str_mv Marin, Marcelo Tadeu
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/7920438802539727
dc.contributor.referee3.fl_str_mv Oliveira, Mauro Schneider
dc.contributor.referee3Lattes.fl_str_mv http://lattes.cnpq.br/7132934163734175
dc.contributor.referee4.fl_str_mv Oliveira, Sara Marchesan de
dc.contributor.referee4Lattes.fl_str_mv http://lattes.cnpq.br/6574555059806902
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/6420900984677569
dc.contributor.author.fl_str_mv Kuhn, Fábio Teixeira
contributor_str_mv Burger, Marilise Escobar
Furian, Ana Flávia
Marin, Marcelo Tadeu
Oliveira, Mauro Schneider
Oliveira, Sara Marchesan de
dc.subject.por.fl_str_mv Ácidos graxos trans
Anfetaminas
Ômega-3
Drogas de abuso
Adicção
topic Ácidos graxos trans
Anfetaminas
Ômega-3
Drogas de abuso
Adicção
Trans fatty acids
Amphetamine
Omega-3
Addiction
CNPQ::CIENCIAS DA SAUDE::FARMACIA
dc.subject.eng.fl_str_mv Trans fatty acids
Amphetamine
Omega-3
Addiction
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS DA SAUDE::FARMACIA
description Polyunsaturated fatty acids (PUFA) are constituents of neuronal membrane phospholipids which play key roles in the development and functioning of the brain. The last decades have been accompanied by changes in dietary habits, especially in Western countries through the industrialization of foods, which contributed to the increased consumption of trans fatty acids (TFA) and omega-6 fatty acid (FA n-6) over AG omega-3 (n-3). Recent studies of our group have shown that such dietary changes can alter the composition of neuronal membrane phospholipids, altering the dopaminergic system, which may facilitate the preference for psychostimulant addictive drugs. This study was conducted through two experimental protocols: 1) adult Wistar rats were divided into four experimental groups were daily supplemented with soybean oil (SO rich in PUFA n-6), fish oil (FO rich in PUFAs n-3) or hydrogenated vegetable fat (HVF, rich in TFAs) and control group (supplemented with water), from pre-conception period until weaning of the 2nd generation, whose offspring remained the same supplements until 40 post-natal day (PND). Male rats born from the 2nd generation were conditioned in protocol preference with amphetamine (AMPH), and subsequently under behavioral observation rather than for drug development of anxiety, assessment of lipid profile of brain tissue, as well as parameters of stress oxidative the same brain areas; 2) adult Wistar rats, divided into three experimental groups were supplemented daily with a mixture of SO and FO which was generating an ideal ratio of PUFA n-6/n-3 (2:1) or HVF and control group (supplemented with water), since the pre-conceptional period until weaning of 1st generation, whose male pups were kept under the same progenitor supplements until 50 post-natal day when they were submitted to a protocol of self-administration of AMPH, followed by behavioral assessments, analysis and molecular incorporation of FA profile in different brain areas. Animals supplemented by 2nd generation HVF showed incorporation of TFA in whole brain, and increased preference for AMPH, indicating the involvement of changes in dopaminergic circuitry. Animals supplemented with HVF 1st generation had a higher frequency of self-administration of AMPH, indicating greater degree of addiction by psychostimulant. The animals supplemented with HVF in both experimental protocols showed a higher degree of anxiety, the two generations of rats showed increased oxidative status, accompanied by molecular damage in dopaminergic brain areas. The results show that chronic consumption of trans fats at the expense of polyunsaturated fatty acids especially the n-3 series, may modify the constitution of lipid membranes and affect neuronal plasticity, modifying dopaminergic neurotransmission, which is strongly associated with the development of addiction by psychostimulant drugs, and anxiety which is one of the symptoms of AMPHaddiction.
publishDate 2015
dc.date.issued.fl_str_mv 2015-07-16
dc.date.accessioned.fl_str_mv 2019-07-26T19:30:16Z
dc.date.available.fl_str_mv 2019-07-26T19:30:16Z
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/1/17570
url http://repositorio.ufsm.br/handle/1/17570
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 cea6b067-f9a7-4654-8ec5-65f1c465c1a8
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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:Manancial - Repositório Digital da UFSM
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