# Multiomic profiling of cell types mediating opioid use disorder in rats

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $129,280

## Abstract

Project Summary
The misuse and abuse of prescription pain relievers, such as oxycodone, contributed to the unprecedented
opioid epidemic in the United States. Despite substantial knowledge of the pharmacokinetic and behavioral
effects of oxycodone in various animal models, only a small number of candidate genes and neuroanatomical
systems affected by opioids have been studied. Recent technological advances in the field of single cell
genomics are promising avenues for the unbiased discovery and characterization of brain cell types that
respond to opioids.
In the parent R01 grant, we leverage a multi-omics methodology (Single Cell Multiome ATAC + Gene
Expression) to map the transcriptome and epigenome from the same cell across thousands of cells in brain
regions relevant to the effects of opioid exposure. To this aim, we will use a rat model of extended access to
oxycodone intravenous self-administration that recapitulates several neuroadaptations also observed in
humans with opioid use disorders (OUD). This approach provides an exceptional opportunity to systematically
explore the cellular diversity of the opioid system and, at the same time, the causative mechanisms that
regulate cellular states based on the associations between epigenetic changes and the expression of target
genes in individual cells. We will integrate this multi-omics methodology with rigorous computational
approaches to explore the cellular organization of the opioid system in multiple brain regions and different
stages of OUD progression.
 In this supplement request, we are extending the studies funded by the parent grant to focus on
glucocorticoid receptor (GR)--regulated enhancers. Specifically, we will generate GR binding profiles by
CUT&RUN and calculate the enrichment in specific cell types by integrating the single-cell omics datasets
produced by the parental R01.

## Key facts

- **NIH application ID:** 11075487
- **Project number:** 3R01DA056602-03S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Giordano De Guglielmo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $129,280
- **Award type:** 3
- **Project period:** 2022-08-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11075487

## Citation

> US National Institutes of Health, RePORTER application 11075487, Multiomic profiling of cell types mediating opioid use disorder in rats (3R01DA056602-03S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11075487. Licensed CC0.

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