Influence of the dopaminergic system, CREB, and transcription factor-B on cocaine neurotoxicity

Detalhes bibliográficos
Autor(a) principal: Planeta, Cleopatra da Silva [UNESP]
Data de Publicação: 2013
Outros Autores: Lepsch, L.b., Alves, R., Scavone, C.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1590/1414-431X20133379
http://hdl.handle.net/11449/109480
Resumo: Cocaine is a widely used drug and its abuse is associated with physical, psychiatric and social problems. Abnormalities in newborns have been demonstrated to be due to the toxic effects of cocaine during fetal development. The mechanism by which cocaine causes neurological damage is complex and involves interactions of the drug with several neurotransmitter systems, such as the increase of extracellular levels of dopamine and free radicals, and modulation of transcription factors. The aim of this review was to evaluate the importance of the dopaminergic system and the participation of inflammatory signaling in cocaine neurotoxicity. Our study showed that cocaine activates the transcription factors NF-κB and CREB, which regulate genes involved in cellular death. GBR 12909 (an inhibitor of dopamine reuptake), lidocaine (a local anesthetic), and dopamine did not activate NF-κB in the same way as cocaine. However, the attenuation of NF-κB activity after the pretreatment of the cells with SCH 23390, a D1 receptor antagonist, suggests that the activation of NF-κB by cocaine is, at least partially, due to activation of D1 receptors. NF-κB seems to have a protective role in these cells because its inhibition increased cellular death caused by cocaine. The increase in BDNF (brain-derived neurotrophic factor) mRNA can also be related to the protective role of both CREB and NF-κB transcription factors. An understanding of the mechanisms by which cocaine induces cell death in the brain will contribute to the development of new therapies for drug abusers, which can help to slow down the progress of degenerative processes.
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spelling Influence of the dopaminergic system, CREB, and transcription factor-B on cocaine neurotoxicityCocaineApoptosisNF-BCREBBDNFNeurotoxicityCocaine is a widely used drug and its abuse is associated with physical, psychiatric and social problems. Abnormalities in newborns have been demonstrated to be due to the toxic effects of cocaine during fetal development. The mechanism by which cocaine causes neurological damage is complex and involves interactions of the drug with several neurotransmitter systems, such as the increase of extracellular levels of dopamine and free radicals, and modulation of transcription factors. The aim of this review was to evaluate the importance of the dopaminergic system and the participation of inflammatory signaling in cocaine neurotoxicity. Our study showed that cocaine activates the transcription factors NF-κB and CREB, which regulate genes involved in cellular death. GBR 12909 (an inhibitor of dopamine reuptake), lidocaine (a local anesthetic), and dopamine did not activate NF-κB in the same way as cocaine. However, the attenuation of NF-κB activity after the pretreatment of the cells with SCH 23390, a D1 receptor antagonist, suggests that the activation of NF-κB by cocaine is, at least partially, due to activation of D1 receptors. NF-κB seems to have a protective role in these cells because its inhibition increased cellular death caused by cocaine. The increase in BDNF (brain-derived neurotrophic factor) mRNA can also be related to the protective role of both CREB and NF-κB transcription factors. An understanding of the mechanisms by which cocaine induces cell death in the brain will contribute to the development of new therapies for drug abusers, which can help to slow down the progress of degenerative processes.Instituto de Ciencias Biomedicas, Universidade de Sao Paulo Departamento de FarmacologiaUniversidade Estadual Paulista Faculdade de Ciencias Farmaceuticas Laboratorio de NeuropsicofarmacologiaUniversidade Estadual Paulista Faculdade de Ciencias Farmaceuticas Laboratorio de NeuropsicofarmacologiaAssociação Brasileira de Divulgação Científica (ABRADIC)Universidade de São Paulo (USP)Universidade Estadual Paulista (Unesp)Planeta, Cleopatra da Silva [UNESP]Lepsch, L.b.Alves, R.Scavone, C.2014-09-30T18:18:23Z2014-09-30T18:18:23Z2013-11-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article909-915application/pdfhttp://dx.doi.org/10.1590/1414-431X20133379Brazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 46, n. 11, p. 909-915, 2013.0100-879Xhttp://hdl.handle.net/11449/10948010.1590/1414-431X20133379S0100-879X2013001100909WOS:000328203500001S0100-879X2013001100909.pdf25147625452809420000-0002-1378-6327SciELOreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengBrazilian Journal of Medical and Biological Research1.492info:eu-repo/semantics/openAccess2024-06-24T14:51:40Zoai:repositorio.unesp.br:11449/109480Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T16:59:44.172953Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Influence of the dopaminergic system, CREB, and transcription factor-B on cocaine neurotoxicity
title Influence of the dopaminergic system, CREB, and transcription factor-B on cocaine neurotoxicity
spellingShingle Influence of the dopaminergic system, CREB, and transcription factor-B on cocaine neurotoxicity
Planeta, Cleopatra da Silva [UNESP]
Cocaine
Apoptosis
NF-B
CREB
BDNF
Neurotoxicity
title_short Influence of the dopaminergic system, CREB, and transcription factor-B on cocaine neurotoxicity
title_full Influence of the dopaminergic system, CREB, and transcription factor-B on cocaine neurotoxicity
title_fullStr Influence of the dopaminergic system, CREB, and transcription factor-B on cocaine neurotoxicity
title_full_unstemmed Influence of the dopaminergic system, CREB, and transcription factor-B on cocaine neurotoxicity
title_sort Influence of the dopaminergic system, CREB, and transcription factor-B on cocaine neurotoxicity
author Planeta, Cleopatra da Silva [UNESP]
author_facet Planeta, Cleopatra da Silva [UNESP]
Lepsch, L.b.
Alves, R.
Scavone, C.
author_role author
author2 Lepsch, L.b.
Alves, R.
Scavone, C.
author2_role author
author
author
dc.contributor.none.fl_str_mv Universidade de São Paulo (USP)
Universidade Estadual Paulista (Unesp)
dc.contributor.author.fl_str_mv Planeta, Cleopatra da Silva [UNESP]
Lepsch, L.b.
Alves, R.
Scavone, C.
dc.subject.por.fl_str_mv Cocaine
Apoptosis
NF-B
CREB
BDNF
Neurotoxicity
topic Cocaine
Apoptosis
NF-B
CREB
BDNF
Neurotoxicity
description Cocaine is a widely used drug and its abuse is associated with physical, psychiatric and social problems. Abnormalities in newborns have been demonstrated to be due to the toxic effects of cocaine during fetal development. The mechanism by which cocaine causes neurological damage is complex and involves interactions of the drug with several neurotransmitter systems, such as the increase of extracellular levels of dopamine and free radicals, and modulation of transcription factors. The aim of this review was to evaluate the importance of the dopaminergic system and the participation of inflammatory signaling in cocaine neurotoxicity. Our study showed that cocaine activates the transcription factors NF-κB and CREB, which regulate genes involved in cellular death. GBR 12909 (an inhibitor of dopamine reuptake), lidocaine (a local anesthetic), and dopamine did not activate NF-κB in the same way as cocaine. However, the attenuation of NF-κB activity after the pretreatment of the cells with SCH 23390, a D1 receptor antagonist, suggests that the activation of NF-κB by cocaine is, at least partially, due to activation of D1 receptors. NF-κB seems to have a protective role in these cells because its inhibition increased cellular death caused by cocaine. The increase in BDNF (brain-derived neurotrophic factor) mRNA can also be related to the protective role of both CREB and NF-κB transcription factors. An understanding of the mechanisms by which cocaine induces cell death in the brain will contribute to the development of new therapies for drug abusers, which can help to slow down the progress of degenerative processes.
publishDate 2013
dc.date.none.fl_str_mv 2013-11-01
2014-09-30T18:18:23Z
2014-09-30T18:18:23Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1590/1414-431X20133379
Brazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 46, n. 11, p. 909-915, 2013.
0100-879X
http://hdl.handle.net/11449/109480
10.1590/1414-431X20133379
S0100-879X2013001100909
WOS:000328203500001
S0100-879X2013001100909.pdf
2514762545280942
0000-0002-1378-6327
url http://dx.doi.org/10.1590/1414-431X20133379
http://hdl.handle.net/11449/109480
identifier_str_mv Brazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 46, n. 11, p. 909-915, 2013.
0100-879X
10.1590/1414-431X20133379
S0100-879X2013001100909
WOS:000328203500001
S0100-879X2013001100909.pdf
2514762545280942
0000-0002-1378-6327
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Brazilian Journal of Medical and Biological Research
1.492
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 909-915
application/pdf
dc.publisher.none.fl_str_mv Associação Brasileira de Divulgação Científica (ABRADIC)
publisher.none.fl_str_mv Associação Brasileira de Divulgação Científica (ABRADIC)
dc.source.none.fl_str_mv SciELO
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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