Research reportInflexible ethanol intake: A putative link with the Lrrk2 pathway

•Lrrk2 gene is overexpressed only in the striatum of the mice from the Inflexible Drinkers group.•Cltc and Actg1 genes are downregulated in the striatum of the Heavy Drinkers group.•Mapt1 and Picalm genes are downregulated in the striatum of both Heavy and Addicted groups.•Lrrk2 pathway potentially plays a major role in the compulsive ethanol intake behaviour.

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.