Inhibition of Lrrk2 reduces ethanol preference in a model of acute exposure in zebrafish

Publication date: Available online 4 February 2020Source: Progress in Neuro-Psychopharmacology and Biological PsychiatryAuthor(s): Isadora Marques Paiva, Luana Martins de Carvalho, Isabela Martins Di Chiaccio, Isadora de Lima Assis, Elena Naranjo Sánchez, Manuel Bernabé Garcia, Felipe Norberto Alves Ferreira, Maria Luisa Cayuela, Luis David Solis Murgas, Ana Lúcia Brunialti GodardAbstractDue to its multifactorial and yet to be fully understood origin, ethanol addiction is a field that still requires studies for the elucidation of novel genes and pathways that potentially influence the establishment and maintenance of addiction-like phenotypes. In this context, the present study aimed to evaluate the role of the LRRK2 pathway in the modulation of ethanol preference behavior in Zebrafish (Danio rerio). Using the behavioral Conditioned Place Preference (CPP) paradigm, we accessed the preference of animals for ethanol. Next, we evaluated the transcriptional regulation of the gene lrrk2 and the receptors drd1, drd2, grin1a, gria2a, and gabbr1b in the zebrafish brain. Additionally, we used a selective inhibitor of Lrrk2 (GNE-0877) to assess the role of this gene in the preference behavior. Our results revealed four distinct ethanol preference phenotypes (Light, Heavy, Negative Reinforcement, and Inflexible), each showing different transcriptional regulation patterns of the drd1, drd2, grin1a, gria2a, and gabbr1b receptors. We showed that the lrrk2 gene was hyperregulated only in...
Source: Progress in Neuro Psychopharmacology and Biological Psychiatry - Category: Psychiatry Source Type: research