Mechanisms of initiation and reversal of drug-seeking behavior induced by prenatal exposure to glucocorticoids
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2012 |
| Outros Autores: | , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/1822/24080 |
Resumo: | We would like to thank the members of the Neuroscience Research Domain at ICVS for all the helpful discussions and suggestions. We are especially thankful to the animal facility caretakers, and to Drs Sara Silva, António Melo and Ana Paula Silva and Dieter Fischer for their help |
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Mechanisms of initiation and reversal of drug-seeking behavior induced by prenatal exposure to glucocorticoidsDNA methylationDopamine receptor 2LevodopaNucleus accumbensMesolimbic circuitPrenatal glucocorticoidsScience & TechnologyWe would like to thank the members of the Neuroscience Research Domain at ICVS for all the helpful discussions and suggestions. We are especially thankful to the animal facility caretakers, and to Drs Sara Silva, António Melo and Ana Paula Silva and Dieter Fischer for their helpStress and exposure to glucocorticoids (GC) during early life render individuals vulnerable to brain disorders by inducing structural and chemical alterations in specific neural substrates. Here we show that adult rats that had been exposed to in utero GCs (iuGC) display increased preference for opiates and ethanol, and are more responsive to the psychostimulatory actions of morphine. These animals presented prominent changes in the nucleus accumbens (NAcc), a key component of the mesolimbic reward circuitry; specifically, cell numbers and dopamine (DA) levels were significantly reduced, whereas DA receptor 2 (Drd2) mRNA expression levels were markedly upregulated in the NAcc. Interestingly, repeated morphine exposure significantly downregulated Drd2 expression in iuGC-exposed animals, in parallel with increased DNA methylation of the Drd2 gene. Administration of a therapeutic dose of L-dopa reverted the hypodopaminergic state in the NAcc of iuGC animals, normalized Drd2 expression and prevented morphine-induced hypermethylation of the Drd2 promoter. In addition, L-dopa treatment promoted dendritic and synaptic plasticity in the NAcc and, importantly, reversed drug-seeking behavior. These results reveal a new mechanism through which drug-seeking behaviors may emerge and suggest that a brief and simple pharmacological intervention can restrain these behaviors in vulnerable individuals.This work was supported by the Institute for the Study of Affective Neuroscience (ISAN). AJR, BC and MC were supported by Fundação para a Ciência e Tecnologia (FCT) fellowshipsNature Publishing GroupUniversidade do MinhoRodrigues, Ana JoãoLeão, PedroPêgo, José M.Cardona, DianaCarvalho, M.Oliveira, MárioCosta, Bruno MarquesCarvalho, Ana Raquel Franky GomesMorgado, PedroAraújo, D.Palha, Joana AlmeidaAlmeida, O. F. X.Sousa, Nuno2012-122012-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/24080eng1359-418410.1038/mp.2011.12621968930info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:40:43Zoai:repositorium.sdum.uminho.pt:1822/24080Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:37:34.917838Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Mechanisms of initiation and reversal of drug-seeking behavior induced by prenatal exposure to glucocorticoids |
| title |
Mechanisms of initiation and reversal of drug-seeking behavior induced by prenatal exposure to glucocorticoids |
| spellingShingle |
Mechanisms of initiation and reversal of drug-seeking behavior induced by prenatal exposure to glucocorticoids Rodrigues, Ana João DNA methylation Dopamine receptor 2 Levodopa Nucleus accumbens Mesolimbic circuit Prenatal glucocorticoids Science & Technology |
| title_short |
Mechanisms of initiation and reversal of drug-seeking behavior induced by prenatal exposure to glucocorticoids |
| title_full |
Mechanisms of initiation and reversal of drug-seeking behavior induced by prenatal exposure to glucocorticoids |
| title_fullStr |
Mechanisms of initiation and reversal of drug-seeking behavior induced by prenatal exposure to glucocorticoids |
| title_full_unstemmed |
Mechanisms of initiation and reversal of drug-seeking behavior induced by prenatal exposure to glucocorticoids |
| title_sort |
Mechanisms of initiation and reversal of drug-seeking behavior induced by prenatal exposure to glucocorticoids |
| author |
Rodrigues, Ana João |
| author_facet |
Rodrigues, Ana João Leão, Pedro Pêgo, José M. Cardona, Diana Carvalho, M. Oliveira, Mário Costa, Bruno Marques Carvalho, Ana Raquel Franky Gomes Morgado, Pedro Araújo, D. Palha, Joana Almeida Almeida, O. F. X. Sousa, Nuno |
| author_role |
author |
| author2 |
Leão, Pedro Pêgo, José M. Cardona, Diana Carvalho, M. Oliveira, Mário Costa, Bruno Marques Carvalho, Ana Raquel Franky Gomes Morgado, Pedro Araújo, D. Palha, Joana Almeida Almeida, O. F. X. Sousa, Nuno |
| author2_role |
author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universidade do Minho |
| dc.contributor.author.fl_str_mv |
Rodrigues, Ana João Leão, Pedro Pêgo, José M. Cardona, Diana Carvalho, M. Oliveira, Mário Costa, Bruno Marques Carvalho, Ana Raquel Franky Gomes Morgado, Pedro Araújo, D. Palha, Joana Almeida Almeida, O. F. X. Sousa, Nuno |
| dc.subject.por.fl_str_mv |
DNA methylation Dopamine receptor 2 Levodopa Nucleus accumbens Mesolimbic circuit Prenatal glucocorticoids Science & Technology |
| topic |
DNA methylation Dopamine receptor 2 Levodopa Nucleus accumbens Mesolimbic circuit Prenatal glucocorticoids Science & Technology |
| description |
We would like to thank the members of the Neuroscience Research Domain at ICVS for all the helpful discussions and suggestions. We are especially thankful to the animal facility caretakers, and to Drs Sara Silva, António Melo and Ana Paula Silva and Dieter Fischer for their help |
| publishDate |
2012 |
| dc.date.none.fl_str_mv |
2012-12 2012-12-01T00:00:00Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
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article |
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publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/24080 |
| url |
http://hdl.handle.net/1822/24080 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
1359-4184 10.1038/mp.2011.126 21968930 |
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info:eu-repo/semantics/openAccess |
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openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Nature Publishing Group |
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Nature Publishing Group |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799132909442957312 |