Cellular prion protein (PrPC) modulates ethanol-induced behavioral adaptive changes in mice

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dc.contributor.authorRial, Daniel
dc.contributor.authorPandolfo, Pablo
dc.contributor.authorBitencourt, Rafael M.
dc.contributor.authorPamplona, Fabricio A.
dc.contributor.authorMoreira, Karin M. [UNIFESP]
dc.contributor.authorHipolide, Debora [UNIFESP]
dc.contributor.authorDombrowski, Patricia A.
dc.contributor.authorDa Cunha, Claudio
dc.contributor.authorWalz, Roger
dc.contributor.authorCunha, Rodrigo A.
dc.contributor.authorTakahashi, Reinaldo N.
dc.contributor.authorPrediger, Rui D.
dc.contributor.institutionUniversidade Federal de Santa Catarina (UFSC)
dc.contributor.institutionUniv Coimbra
dc.contributor.institutionUniversidade Federal Fluminense (UFF)
dc.contributor.institutionDOr Inst Res & Educ
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniversidade Federal do Paraná (UFPR)
dc.date.accessioned2016-01-24T14:37:48Z
dc.date.available2016-01-24T14:37:48Z
dc.date.issued2014-09-01
dc.description.abstractChronic consumption of drugs with addictive potential induces profound synaptic changes in the dopaminergic mesocorticolimbic pathway that underlie the long-term behavioral alterations seen in addicted subjects. Thus, exploring modulation systems of dopaminergic function may reveal novel targets to interfere with drug addiction. We recently showed that cellular prion protein (PrPC) affects the homeostasis of the dopaminergic system by interfering with dopamine synthesis, content, receptor density and signaling pathways in different brain areas. Here we report that the genetic deletion of PrPC modulates ethanol (EtOH)-induced behavioral alterations including the maintenance of drug seeking, voluntary consumption and the development of EtOH tolerance, all pivotal steps in drug addiction. Notably, these behavioral changes were accompanied by a significant depletion of dopamine levels in the prefrontal cortex and reduced dopamine D-1 receptors in PrPC knockout mice. Furthermore, the pharmacological blockade of dopamine D-1 receptors, but not D-2 receptors, attenuated the abnormal EtOH consumption in PrPC knockout mice. Altogether, these findings provide new evidence that the PrPC/dopamine interaction plays a pivotal role in EtOH addictive properties in mice. (C) 2014 Elsevier B.V. All rights reserved.en
dc.description.affiliationUniv Fed Santa Catarina, Ctr Ciencias Biol, Dept Farmacol, Florianopolis, SC, Brazil
dc.description.affiliationUniv Coimbra, CNC Ctr Neurosci & Cell Biol, P-3000 Coimbra, Portugal
dc.description.affiliationUniv Fed Fluminense, Inst Biol, Dept Neurobiol, Niteroi, RJ, Brazil
dc.description.affiliationDOr Inst Res & Educ, Rio de Janeiro, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, UNIFESP, Dept Psicobiol, São Paulo, Brazil
dc.description.affiliationUniv Fed Parana, UFPR, Dept Farmacol, BR-80060000 Curitiba, Parana, Brazil
dc.description.affiliationUniv Fed Santa Catarina, Univ Hosp, Ctr Neurociencias Aplicadas CeNAp, Florianopolis, SC, Brazil
dc.description.affiliationUniv Coimbra, FMUC Fac Med, P-3000 Coimbra, Portugal
dc.description.affiliationUnifespUniversidade Federal de São Paulo, UNIFESP, Dept Psicobiol, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipPrograma de Apoio aos Nucleos de Excelencia (PRONEX-NENASC Project)
dc.description.sponsorshipFundacao de Apoio a Pesquisa do Estado de Santa Catarina (FAPESC)
dc.description.sponsorshipFundacao para a Ciencia e Tecnologia (Portugal)
dc.description.sponsorshipIDFundacao para a Ciencia e Tecnologia (Portugal): PTDC/SAU-NMC/114810/2009
dc.format.extent325-332
dc.identifierhttp://dx.doi.org/10.1016/j.bbr.2014.05.067
dc.identifier.citationBehavioural Brain Research. Amsterdam: Elsevier B.V., v. 271, p. 325-332, 2014.
dc.identifier.doi10.1016/j.bbr.2014.05.067
dc.identifier.issn0166-4328
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/38154
dc.identifier.wosWOS:000340323000043
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofBehavioural Brain Research
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectCellular prion protein (PrPC)en
dc.subjectEthanolen
dc.subjectDopamineen
dc.subjectBehavioren
dc.subjectConsumptionen
dc.subjectRapid toleranceen
dc.titleCellular prion protein (PrPC) modulates ethanol-induced behavioral adaptive changes in miceen
dc.typeinfo:eu-repo/semantics/article
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