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Behav Brain Res. 2014 Sep 1;271:325-32. doi: 10.1016/j.bbr.2014.05.067. Epub 2014 Jun 26.

Cellular prion protein (PrP(C)) modulates ethanol-induced behavioral adaptive changes in mice.

Author information

1
Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis, SC, Brazil; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Portugal. Electronic address: rialdaniel@gmail.com.
2
Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis, SC, Brazil; Departamento de Neurobiologia, Instituto de Biologia, Universidade Federal Fluminense, Niterói, RJ, Brazil.
3
Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis, SC, Brazil.
4
Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis, SC, Brazil; D'Or Institute for Research and Education, Rio de Janeiro, Brazil.
5
Departamento de Psicobiologia, Universidade Federal de São Paulo, UNIFESP, São Paulo, SP, Brazil.
6
Departamento de Farmacologia, Universidade Federal do Paraná, UFPR, Curitiba, PR, Brazil.
7
Centro de Neurociências Aplicadas (CeNAp), Hospital Universitário, Universidade Federal de Santa Catarina, UFSC, Florianópolis, SC, Brazil.
8
CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; FMUC - Faculty of Medicine, University of Coimbra, Portugal.
9
Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis, SC, Brazil; Centro de Neurociências Aplicadas (CeNAp), Hospital Universitário, Universidade Federal de Santa Catarina, UFSC, Florianópolis, SC, Brazil.

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 (PrP(C)) 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 PrP(C) 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 D1 receptors in PrP(C) knockout mice. Furthermore, the pharmacological blockade of dopamine D1 receptors, but not D2 receptors, attenuated the abnormal EtOH consumption in PrP(C) knockout mice. Altogether, these findings provide new evidence that the PrP(C)/dopamine interaction plays a pivotal role in EtOH addictive properties in mice.

KEYWORDS:

Behavior; Cellular prion protein (PrP(C)); Consumption; Dopamine; Ethanol; Rapid tolerance

PMID:
24975422
DOI:
10.1016/j.bbr.2014.05.067
[Indexed for MEDLINE]
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