GWAS on socially-acquired nicotine self-administration
We are part of the NIDA center for GWAS in outbred rats. Clinical studies have demonstrated that heritability is ~50% for various smoking behaviors. However, most of the genetic factors determining smoking behavior remain unknown. The heterogenous stock (HS) rats are the result of more than 60 generations of intercrossing of 8 inbred rat strains and are particularly suitable for fine genetic mapping studies. The primary goal of study is to phenotype 1,600 HS rats provided by the breeding Core (Dr. Leah Solberg Woods, Medical College of Wisconsin) on socially-acquired nicotine self-administration in four years. We will use adolescent HS rats bred locally to capture the role of this critical brain development stage on smoking initiation. We will also test these HS rats on contextual-cue induced reinstatement of drug seeking. Data on several social and emotional traits will be obtained before self-administration starts. DNA sample from each rat will be sent to the Sequencing Core (University of Chicago) for genotyping. The quantitative behavioral measures will be sent to Research Project 4 (Dr. Abraham Palmer, University of Chicago) to perform a genome-wide association study on nicotine intake and reinstatement of nicotine seeking. Another goal of this Research Project is to use laser capture microdissection (LCM) to precisely collect tissue from 72 HS brains. Four brain regions that are critical for the behaviors investigated by the center will be targeted. RNA extracted from these samples will be sequenced by the Sequencing Core. Research Project 4 will analyze these gene expression data and integrate the results with the behavioral and genomic findings.