title: Inflexible ethanol intake: A putative link with the Lrrk2 pathway.
abstract: Alcoholism is a complex multifactorial disorder with a strong genetic influence. Although several studies have shown the impact of high ethanol intake on the striatal gene expression, few have addressed the relationship between the patterns of gene expression underlying the compulsive behaviour associated with the two major concerns in addiction: the excessive drug consumption and relapsing. In this study, we used a chronic three-bottle free-choice murine model to address striatal transcript regulation among animals with different ethanol intakes and preferences: Light Drinkers (preference for water throughout the experiment), Heavy Drinkers (preference for ethanol with a non-compulsive intake) and Inflexible Drinkers (preference for ethanol and simultaneous loss of control over the drug intake). Our aim was to correlate the intake patterns observed in this model with gene expression changes in the striatum, a brain region critical for the development of alcohol addiction. We found that the transcripts of the Lrrk2 gene, which encodes a multifunctional protein with kinase and GTPase activities, is upregulated only in Inflexible Drinkers suggesting, for the first time, that the Lrrk2 pathway plays a major role in the compulsive ethanol intake behaviour of addicted subjects.
authors.affiliation: Departmento de Biologia Geral, Universidade Federal de Minas Gerais, Pampulha, Belo Horizonte, MG CEP 31270-901, Brazil.
authors.forename: Daniel Almeida
authors.initials: DA
authors.lastname: da Silva E Silva
authors.affiliation: Programa de Pós-Graduação em Neurociências, Faculdade de Filosofia de Ciências Humanas, Universidade Federal de Minas Gerais, MG 31270-901, Brazil.
authors.forename: Andrea
authors.initials: A
authors.lastname: Frozino Ribeiro
authors.affiliation: Departmento de Biologia Geral, Universidade Federal de Minas Gerais, Pampulha, Belo Horizonte, MG CEP 31270-901, Brazil.
authors.forename: Samara
authors.initials: S
authors.lastname: Damasceno
authors.affiliation: Departmento de Genética Médica, Faculdade de Ciências Medicas, Universidade de Campinas, Tessália Vieira de Camargo, Cidade Universitária Zeferino Vaz, Campinas, SP, Brazil.
authors.forename: Cristiane S
authors.initials: CS
authors.lastname: Rocha
authors.affiliation: Departmento de Genética Médica, Faculdade de Ciências Medicas, Universidade de Campinas, Tessália Vieira de Camargo, Cidade Universitária Zeferino Vaz, Campinas, SP, Brazil.
authors.forename: Alexandre H
authors.initials: AH
authors.lastname: Berenguer de Matos
authors.affiliation: Departamento de Farmacologia, Jardim das Américas, Universidade Federal do Paraná, P.O. Box 19031, Curitiba, PR 81531-990, Brazil.
authors.forename: Roseli
authors.initials: R
authors.lastname: Boerngen-Lacerda
authors.affiliation: Departmento de Biologia Geral, Universidade Federal de Minas Gerais, Pampulha, Belo Horizonte, MG CEP 31270-901, Brazil; Departamento de Farmacologia, Jardim das Américas, Universidade Federal do Paraná, P.O. Box 19031, Curitiba, PR 81531-990, Brazil.
authors.forename: Diego
authors.initials: D
authors.lastname: Correia
authors.affiliation: Departmento de Biologia Geral, Universidade Federal de Minas Gerais, Pampulha, Belo Horizonte, MG CEP 31270-901, Brazil. Electronic address: brunialt@ufmg.br.
authors.forename: Ana Lúcia
authors.initials: AL
authors.lastname: Brunialti Godard
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics*; D000437:Alcoholism / Q000235:genetics*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage*; D015870:Gene Expression; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000378:metabolism*; D008297:Male; D051379:Mice; D040081:Protein Array Analysis; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000431:Ethanol; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; C495279:Lrrk2 protein, mouse
keywords: Addiction; Chronic ethanol intake; Inflexible drinking; Leucine-rich-repeat kinase II (Lrrk2); Striatum transcriptome; Three-bottle free-choice murine model