Influência dos ácidos graxos da dieta sobre parâmetros de adicção à anfetamina em ratos: aspectos comportamentais, bioquímicos e moleculares
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | 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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Influência 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 molecularÁcidos graxos transAnfetaminasÔmega-3Drogas de abusoAdicçãoTrans fatty acidsAmphetamineOmega-3AddictionCNPQ::CIENCIAS DA SAUDE::FARMACIAPolyunsaturated 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.Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, FAPERGS, Brasil.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.Universidade Federal de Santa MariaBrasilFarmacologiaUFSMPrograma de Pós-Graduação em FarmacologiaCentro de Ciências da SaúdeBurger, 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/6574555059806902Kuhn, Fábio Teixeira2019-07-26T19:30:16Z2019-07-26T19:30:16Z2015-07-16info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/17570porAttribution-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:UFSM2019-07-27T06:02:32Zoai:repositorio.ufsm.br:1/17570Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2019-07-27T06:02:32Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Influência dos ácidos graxos da dieta sobre parâmetros de adicção à anfetamina em ratos: aspectos comportamentais, bioquímicos e moleculares 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.none.fl_str_mv |
Burger, Marilise Escobar http://lattes.cnpq.br/9128090974948413 Furian, Ana Flávia http://lattes.cnpq.br/0865191340133424 Marin, Marcelo Tadeu http://lattes.cnpq.br/7920438802539727 Oliveira, Mauro Schneider http://lattes.cnpq.br/7132934163734175 Oliveira, Sara Marchesan de http://lattes.cnpq.br/6574555059806902 |
dc.contributor.author.fl_str_mv |
Kuhn, Fábio Teixeira |
dc.subject.por.fl_str_mv |
Ácidos graxos trans Anfetaminas Ômega-3 Drogas de abuso Adicção Trans fatty acids Amphetamine Omega-3 Addiction CNPQ::CIENCIAS DA SAUDE::FARMACIA |
topic |
Ácidos graxos trans Anfetaminas Ômega-3 Drogas de abuso Adicção Trans fatty acids Amphetamine Omega-3 Addiction 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.none.fl_str_mv |
2015-07-16 2019-07-26T19:30:16Z 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.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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1805922162800852992 |