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

dc.contributorUniversidade Estadual Paulista (UNESP)
dc.creatorPlaneta, Cleopatra da Silva
dc.creatorLepsch, L.b.
dc.creatorAlves, R.
dc.creatorScavone, C.
dc.date2014-09-30T18:18:23Z
dc.date2016-10-25T19:44:20Z
dc.date2014-09-30T18:18:23Z
dc.date2016-10-25T19:44:20Z
dc.date2013-11-01
dc.date.accessioned2017-04-06T05:49:42Z
dc.date.available2017-04-06T05:49:42Z
dc.identifierBrazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 46, n. 11, p. 909-915, 2013.
dc.identifier0100-879X
dc.identifierhttp://hdl.handle.net/11449/109480
dc.identifierhttp://acervodigital.unesp.br/handle/11449/109480
dc.identifier10.1590/1414-431X20133379
dc.identifierS0100-879X2013001100909
dc.identifierWOS:000328203500001
dc.identifierS0100-879X2013001100909.pdf
dc.identifierhttp://dx.doi.org/10.1590/1414-431X20133379
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/920304
dc.descriptionCocaine 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.
dc.languageeng
dc.publisherAssociação Brasileira de Divulgação Científica (ABRADIC)
dc.relationBrazilian Journal of Medical and Biological Research
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectCocaine
dc.subjectApoptosis
dc.subjectNF-B
dc.subjectCREB
dc.subjectBDNF
dc.subjectNeurotoxicity
dc.titleInfluence of the dopaminergic system, CREB, and transcription factor-B on cocaine neurotoxicity
dc.typeOtro


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