# Use of Next-Gen Sequencing to Identify Genetic Variants that Influence compulsiveOxycodone Intake in Outbred Rats

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $629,605

## Abstract

Project SummaryAbstract
Epidemiological studies suggest that genetic variability significantly contributes (20-60%) to the analgesic
response to opioids and vulnerability to opioid use disorder. However, genome-wide association studies
(GWASs) in humans have only begun to identify specific genes that confer this risk. One major impediment to
studies of opioid use disorder is the complexity of the phenotype and lack of control of environmental variables.
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. We will use the most relevant animal model of
oxycodone use disorder (i.e., escalation of intravenous oxycodone self-administration) and highly standardized
measures of compulsive oxycodone self-administration combined with longitudinal assessments of pain
thresholds. 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.

## Key facts

- **NIH application ID:** 9847956
- **Project number:** 5U01DA044451-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Olivier George
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $629,605
- **Award type:** 5
- **Project period:** 2019-08-13 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9847956

## Citation

> US National Institutes of Health, RePORTER application 9847956, Use of Next-Gen Sequencing to Identify Genetic Variants that Influence compulsiveOxycodone Intake in Outbred Rats (5U01DA044451-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9847956. Licensed CC0.

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