Genetics of Compulsive Oxycodone Intake in HS 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 greater vulnerability to compulsive oxycodone use, tolerance to the analgesic effects of oxycodone, development of withdrawal-induced hyperalgesia, and sensitivity to FDA-approved medications by performing a GWAS in N/NIH heterogeneous stock rats. 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 oxycodone use and its comorbidity with hyperalgesia in male and female outbred rats, (2) identify genes associated with compulsive oxycodone use, the preclinical efficacy of current medication (e.g., buprenorphine), and the analgesic/hyperalgesic effects of chronic oxycodone use, and (3) facilitate follow-up studies by creating a repository that contains brain and blood with a variety of tissue preservation protocols that will facilitate follow-up and replicative studies by allowing the generation of induced pluripotent stem cells and 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 Phenotypes Protocols.io
Methods for Omics