title: Cellular prion protein (PrP(C)) modulates ethanol-induced behavioral adaptive changes in mice.
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.
authors: 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.
authors: Daniel
authors: D
authors: Rial
authors: 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.
authors: Pablo
authors: P
authors: Pandolfo
authors: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis, SC, Brazil.
authors: Rafael M
authors: RM
authors: Bitencourt
authors: 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.
authors: Fabrício A
authors: FA
authors: Pamplona
authors: Departamento de Psicobiologia, Universidade Federal de São Paulo, UNIFESP, São Paulo, SP, Brazil.
authors: Karin M
authors: KM
authors: Moreira
authors: Departamento de Psicobiologia, Universidade Federal de São Paulo, UNIFESP, São Paulo, SP, Brazil.
authors: Débora
authors: D
authors: Hipolide
authors: Departamento de Farmacologia, Universidade Federal do Paraná, UFPR, Curitiba, PR, Brazil.
authors: Patrícia A
authors: PA
authors: Dombrowski
authors: Departamento de Farmacologia, Universidade Federal do Paraná, UFPR, Curitiba, PR, Brazil.
authors: Claudio
authors: C
authors: Da Cunha
authors: Centro de Neurociências Aplicadas (CeNAp), Hospital Universitário, Universidade Federal de Santa Catarina, UFSC, Florianópolis, SC, Brazil.
authors: Roger
authors: R
authors: Walz
authors: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; FMUC - Faculty of Medicine, University of Coimbra, Portugal.
authors: Rodrigo A
authors: RA
authors: Cunha
authors: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis, SC, Brazil.
authors: Reinaldo N
authors: RN
authors: Takahashi
authors: 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.
authors: Rui D
authors: RD
authors: Prediger
mesh_terms: D000223:Adaptation, Psychological / Q000187:drug effects*; D000428:Alcohol Drinking / Q000235:genetics / Q000523:psychology*; D000818:Animals; D004298:Dopamine / Q000172:deficiency*; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018621:PrPC Proteins / Q000172:deficiency*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism
chemical_list: D018621:PrPC Proteins; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D000431:Ethanol; D004298:Dopamine
keywords: Behavior; Cellular prion protein (PrP(C)); Consumption; Dopamine; Ethanol; Rapid tolerance