Genetics of Compulsive Cocaine Intake in Rats
We propose a complementary approach that leverages a multidisciplinary, highly collaborative consortium that combines next-generation sequencing with state-of-the-art behavioral screening in a unique, genetically diverse, nonhuman animal model. The primary goal of this proposal is to identify gene variants that are associated with increased vulnerability to compulsive cocaine use by performing a GWAS in N/NIH heterogeneous stock rats. We will use the most relevant animal model of cocaine use disorder (i.e., escalation of intravenous cocaine self-administration) and highly standardized measures of controlled and compulsive cocaine self-administration. This project is likely to have a sustained and powerful impact on the field because it will (1) characterize the transition from controlled to compulsive cocaine use in male and female outbred rats, (2) identify genes associated with compulsive cocaine use, (3) create the CocainBioBank which will provide free access to brain, kidney, liver, spleen, ovary, testis, adrenal, and blood samples with a variety of tissue preservation protocols that will allow the generation of induced pluripotent stem cells as well as neuroanatomical, molecular, biochemical, and pharmacological studies on behaviorally/genetically characterized animals.
Methods for genotype
Low-coverage WGS based on Riptide library preparation(pulication in progress)
Methods for Phenotypes
Protocols for PhenotypesProtocols.io
Methods for Omics