# Center for Genetic Studies of Drug Abuse in Outbred Rats

> **NIH NIH P50** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $2,985,563

## Abstract

Project Summary (Overall)
 The purpose of this renewal application is to continue the successful activities of our center, which uses
quantitative genetic techniques to study the genetic basis of drug abuse-related behaviors in outbred rats.
When our center was initially funded in June 2014, our goal was to develop outbred N/NIH heterogeneous
stock (HS) rats as a platform for genetic studies of behaviors that were difficult or impossible to study in mice.
The first four years of funding have allowed us to establish a vibrant community of investigators using HS rats
to study drug abuse and other traits, which we refer to as an ecosystem. This ecosystem includes both the
investigators who are directly involved in this renewal application and many others who have obtained
separate funding, some from NIDA, and some from other sources. The growth of this ecosystem reflects one of
the ways that our center has served as national resource. We are proposing three projects that involved
phenotyping HS rats for a variety of traits, including intravenous cocaine and nicotine self-administration,
response to novelty, social behavior, reaction time, and delay discounting. Two of those projects are
continuations from the prior funding period and are designed to increase our sample size from 1,600 to 3,200
rats per phenotype. We present data showing that such an increase produces an exponential increase in the
number of significant findings. This approach parallels human genetics studies of SUD, which have also
benefited tremendously from larger sample sizes. We will use these data to conduct genome-wide association
studies (GWAS) and a suite of related techniques. In addition, we will measure gene expression in behaviorally
naïve rats using RNASeq and use those data to identify expression quantitative trait loci (eQTLs). We will then
integrate GWAS and eQTL data in an effort to identify specific genes that influence the behavioral phenotypes.
Many of the behavioral domains being studied are known to be sexually dimorphic; our study will use both
male and female rats, which will allow us to identify sex differences and sex by genotype interactions. We will
also study genetic correlations, perform phenome-wide association studies (PheWAS), transcriptome wide
association studies (TWAS) and explore a novel strategy called polygenic transcriptomic risk scores (PTRS),
that is intended to allow translation of polygenic signals across species. Project 4 will use a network-based
approach to extend our GWAS to account for known biological networks. This proposed renewal also includes
a pilot project core to support new directions and take advantage of unforeseen opportunities. Finally we
propose an administrative core that supports many activities of the center, including educational, career
development and public outreach. The results of these studies will enhance our understanding of the role of
genes in a range of psychologically complex behaviors and will provide nov...

## Key facts

- **NIH application ID:** 9971494
- **Project number:** 5P50DA037844-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Abraham A. Palmer
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,985,563
- **Award type:** 5
- **Project period:** 2014-06-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971494

## Citation

> US National Institutes of Health, RePORTER application 9971494, Center for Genetic Studies of Drug Abuse in Outbred Rats (5P50DA037844-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9971494. Licensed CC0.

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