# Single-cell resolution analysis of chromatin accessibility and gene expression changes in a model of drug addiction

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $710,169

## Abstract

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Project Summary
Every year, more than 100 Americans a day die after overdosing on opiates. Addiction to opioids, including
prescription drug such as oxycodone, and illicit drugs such a s heroin and fentanyl, is a national crisis that
affects public health and the economy. Thus, there is an urgent need to develop better treatments for opiate
addiction, which requires a better understanding of its biological basis. The primary goal of our proposal is to
identify cell types and cell type-specific gene expression patterns associated with higher vulnerability to
compulsive oxycodone use in an unbiased and quantitative way. We will accomplish this goal by implementing
single-cell sequencing assays to measure gene expression and chromatin accessibility in thousands of
individual cells in a single experiment. We will use brains of N/NIH heterogeneous stock (HS) rats that have
undergone the extended access to oxycodone self-administration procedure. We focus on HS rats because
they are genetically diverse and exhibit an exceptional behavioral repertoire. These rats are characterized as
vulnerable or resistant to oxycodone compulsive intake based on advanced analysis of addiction-like
behavioral traits, including tolerance, dependence, motivation, and compulsive drug intake. This behavioral
paradigm recapitulates many of the key neuroadaptations observed in human addiction and has high face,
predictive, and construct validity for oxycodone use disorders. This project takes advantage of a brain tissue
repository of HS rats that have been genotyped and characterized as vulnerable and resistant to compulsive
oxycodone use. The oxycodone biobank (www.OxycodoneBioBank.org) will provide the samples to be used in
this project. We will focus on the nucleus accumbens, a brain region involved in the transition from moderate to
excessive drug use. Our preliminary studies on single-cell analysis of the cerebral cortex provide a compelling
strategy to study the biological basis of opiate addiction. We propose: 1) to use single-cell RNA-seq to identify
gene expression changes in brains of HS rats that are characterized as prone or resistant to oxycodone
compulsive use (Specific Aim 1); 2) to use single-cell ATAC-seq to identify changes in chromatin accessibility
and transcription factors binding sites in the same population of HS rats (Specific Aim 2); 3) to use H3K27Ac-
PLAC-seq to link distal regulatory elements to target genes involved in oxycodone addiction-related behaviors
(Specific Aim 3). This project will benefit from multiple expertise and will leverage existing resources, including
those provided by the oxycodone biobank (U01DA044451) and the NIDA center for GWAS in outbred rats
(P50DA037844). We believe that the proposed studies have the potential to lead to groundbreaking
discoveries in the mechanistic bases of opioids addiction. The integrative analysis of our sequencing datasets
will provide considerable new insights concerning the contribution of disti...

## Key facts

- **NIH application ID:** 9897370
- **Project number:** 1U01DA050239-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Francesca Telese
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $710,169
- **Award type:** 1
- **Project period:** 2020-05-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9897370

## Citation

> US National Institutes of Health, RePORTER application 9897370, Single-cell resolution analysis of chromatin accessibility and gene expression changes in a model of drug addiction (1U01DA050239-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9897370. Licensed CC0.

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