Cocaine/saline study in HMDP mouse strains of PFC/NAc

This project will chart with high-resolution the genetic pathways that give rise to defined clinical phenotypes related to cocaine addiction. We will utilize the power of the hybrid mouse diversity panel (HMDP), combined with high quality behavioral phenotyping and massive-scale RNA sequencing, to trace the interconnections from DNA to RNA to clinical trait and provide layered information on the mechanisms of cocaine abuse. The HMDP consists of 100 inbred and recombinant inbred strains and has a wide array of meiotic breakpoints. The panel has been densely genotyped with more than 200,000 single nucleotide polymorphisms (SNPs), allowing very fine mapping of quantitative trait loci (QTLs). Further, the HMDP is genetically stable and renewable and can be assayed for multiple phenotypes, yielding cumulative biological information. We will expand our previous HMDP-based studies of cocaine abuse-related traits by adding massive-scale RNA sequencing (RNA-Seq), in order to detail the genetic control of the pathways to addiction. Use of hybrid mouse diversity panel to map genetic pathways related to cocaine addiction