Study title

Genomic analysis of avoidance learning in addiction

Description

Addictions are among the heritable of human neuropsychiatric disorders, but human genetic studies have been hampered by the complexity of human genetics, as well as the sheer behavioral complexity of the addictive process. We address these shortcomings by studying heterogeneous stock (HS) rats. Our preliminary findings show that even though addiction is often viewed as aberrant reward learning, much individual variation in addiction propensity is actually due to differences in avoidance learning. We seek to identify the genetic differences underlying these two distinct addiction vulnerability phenotypes using a genome-wide association screen (GWAS) to identify candidate genes in HS rats, followed by eQTL analysis on gene expression in the RMTg and afferent circuits that drive these behaviors. This project will identify candidate addiction-related genes using a highly innovative combination of powerful behavioral tests, extensive neural circuitry knowledge, and the Palmer lab’s groundbreaking sequencing and analytical approaches.

Funding sources

U01DA044468

Keywords

RNA-Seq

Avoidance-Learning

Methods for genotype

Low-coverage WGS based on Riptide library preparation (pulication in progress)

Methods for Phenotypes

Runway operant self-administration task in which animals traverse a five-foot corridor to receive single doses of cocaine;

Locomotor responses to a novel apparatus;

Progressive ratio food-seeking task;

Punishment resistance task in which we measured the amount of shock the rats would tolerate to obtain food pellets;

Methods for Omics