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

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

Author Rial, Daniel Google Scholar
Pandolfo, Pablo Google Scholar
Bitencourt, Rafael M. Google Scholar
Pamplona, Fabricio A. Google Scholar
Moreira, Karin M. Autor UNIFESP Google Scholar
Hipolide, Debora Autor UNIFESP Google Scholar
Dombrowski, Patricia A. Google Scholar
Da Cunha, Claudio Google Scholar
Walz, Roger Google Scholar
Cunha, Rodrigo A. Google Scholar
Takahashi, Reinaldo N. Google Scholar
Prediger, Rui D. Google Scholar
Institution Universidade Federal de Santa Catarina (UFSC)
Univ Coimbra
Universidade Federal Fluminense (UFF)
DOr Inst Res & Educ
Universidade Federal de São Paulo (UNIFESP)
Universidade Federal do Paraná (UFPR)
Abstract Chronic 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.
Keywords Cellular prion protein (PrPC)
Rapid tolerance
Language English
Sponsor Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Programa de Apoio aos Nucleos de Excelencia (PRONEX-NENASC Project)
Fundacao de Apoio a Pesquisa do Estado de Santa Catarina (FAPESC)
Fundacao para a Ciencia e Tecnologia (Portugal)
Grant number Fundacao para a Ciencia e Tecnologia (Portugal): PTDC/SAU-NMC/114810/2009
Date 2014-09-01
Published in Behavioural Brain Research. Amsterdam: Elsevier B.V., v. 271, p. 325-332, 2014.
ISSN 0166-4328 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 325-332
Origin http://dx.doi.org/10.1016/j.bbr.2014.05.067
Access rights Closed access
Type Article
Web of Science ID WOS:000340323000043
URI http://repositorio.unifesp.br/handle/11600/38154

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