# The Genetic Basis of Opioid Dependence Vulnerablility in a Rodent Model

> **NIH NIH U01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2020 · $852,370

## Abstract

PROJECT SUMMARY
Opioid abuse is a serious global problem that affects the health, social and economic welfare of all societies.
Opioid use disorder (OUD) is a medical condition characterized by the compulsive use of opioids despite adverse
consequences from continued use and the development of a withdrawal syndrome when opioid use ends. OUD
involves both addiction to and dependence upon opioids. Opioids include prescription pharmaceuticals such as
morphine, codeine, oxycodone and hydrocodone as well as illicit drugs such as heroin. Although animal models
provide a rigorous, convenient means to precisely control environmental context and drug exposure, and assess
behavioral, genomic, biochemical and cognitive changes, effective utilization of such models as an efficient proxy
for human addiction remains challenging. The identities of gene variants that mediate behavioral differences in
laboratory animals remain largely unknown, greatly limiting interpretation of physiologic differences and
understanding of the environmental effects on drug abuse, and hindering translation of genetic findings to
humans. This limitation highlights the urgent need for an integrated genomic characterization of a robust animal
model of opioid abuse. The goal of this project is to exploit an outbred animal model of opioid abuse research,
coupled with comprehensive genomic characterization, to improve detection of the underlying phenotypic and
genomic changes associated with transition to opioid abuse. The project will engage an international
multidisciplinary team of experts in the areas of addiction science and behavioral studies, neurobiology, rodent
genetics, computational genomics, bioinformatics, and high throughput computing and data modeling to
accomplish three Specific Aims. In Aim 1, we will exploit a validated outbred animal model of heroin self-
administration with extended access that produces behavioral phenotypes consistent with increased drug
consumption, accelerated motivation for drug intake and elevated drug-seeking in periods of drug absence.
Animals at two distinct geographical sites (one in the USA and one in Europe) will be stratified across a
‘vulnerable’  ‘resistant’ spectrum with the objective of performing genetic screening on all individuals. In Aim
2, we will carry out a genome-wide association study (GWAS) using genotyping by sequencing (GBS) on 1,000
animals sampled from the two locations. Validation of the most significant genetic variants will be performed in
an independent validation cohort of 100 animals. In Aim 3, we will assess the genomic impact of the genetic
variants uncovered in Aim 2 via high throughput RNA sequencing to assess gene expression of relevant
functional genes and uncover expression quantitative trait loci (eQTLs). Chromosome conformation capture (3C)
will be used to physically link an eQTL with its target gene assigning causality to a variant and its regulated gene.

## Key facts

- **NIH application ID:** 9982281
- **Project number:** 5U01DA045300-03
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Dongjun Chung
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $852,370
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982281

## Citation

> US National Institutes of Health, RePORTER application 9982281, The Genetic Basis of Opioid Dependence Vulnerablility in a Rodent Model (5U01DA045300-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9982281. Licensed CC0.

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