Project title: The Genetics of Addiction: Identification of Genetic and Genomic Variants by Next-Generation Sequencing in Non-Human Animals
Summary: We aim to use genetic and developmental analysis of zebrafish to identify novel alleles and molecular mechanisms contributing to core behaviours predictive of vulnerability to drug addiction: drug seeking and impulse control, with a focus on nicotine addiction. Addiction is one of the major mental health disorders in the world. Despite the many novel insights from addiction research, currently available treatments are still not very effective and addiction including smoking remains a chronic-intermittent disorder for the vast majority of patients seeking treatment. Although estimates vary, there is clear evidence for a genetic link between vulnerability to addiction, as well as quit rates and likelihood to relapse. Furthermore, genetic factors are partly responsible for, not only the comorbidity across addictions, but also between addictions and other mental illness. Here we aim to use screens of ENU-mutagenized zebrafish lines and analysis of empirically derived candidate mutants to identify genes affecting two addiction phenotypes: nicotine reward and impulsivity. There is strong evidence that the neural circuits that underlie reward and addiction are evolutionarily conserved between humans and zebrafish. These findings support the argument that zebrafish screens can be used to identify genes and pathways for reward and addiction, as well as potential therapeutics, as for other human disorders.