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

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $554,504

## Abstract

Project Summary
The misuse and abuse of prescription pain relievers, such as oxycodone, contributed to the unprecedented
opioid epidemic in the United States. The opioid crisis has devastating consequences on public health including
a surge in opioid misuse and related overdoses. Research is urgently needed to develop better treatments for
opiate addiction.
 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 response to this RFA, we leverage an innovative 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 innovative multi-omics methodology with rigorous computational
approaches to explore the cellular organization the opioid system in multiple brain regions and different stages
of OUD progression (initial exposure, escalation of use, acute withdrawal, prolonged abstinence, and cue-
induced relapse).
 We have provided strong preliminary that support the feasibility of our proposed plan for the following
aims. In Aim 1, we will collect brain tissues at different stages of the extended access to oxycodone intravenous
self-administration (ivsa) protocol and we will generate single cell genomics data from both male and female
rats that are exposed to either saline or oxycodone. In Aim 2, we will integrate these transcriptomic and
epigenomic datasets to identify changes in cellular states, genes and upstream regulators that are associated with
different stages of oxycodone use. This approach will facilitate the identification of linkages between cis-
regulatory elements and target genes. In Aim 3, we will validate key cell type-specific findings by RNA-FISH
and identify the top 3 target genes for functional validation. To this aim, we will use a viral-mediated CRISPR-
Cas9 system to modulate addictive behaviors in rat models of oxycodone self-administration. The results of this
study will enable future studies that may identify new targets for treatment and prevention of OUD.

## Key facts

- **NIH application ID:** 10510294
- **Project number:** 1R01DA056602-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Francesca Telese
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $554,504
- **Award type:** 1
- **Project period:** 2022-08-15 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10510294

## Citation

> US National Institutes of Health, RePORTER application 10510294, Multiomic profiling of cell types mediating opioid use disorder in rats (1R01DA056602-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10510294. Licensed CC0.

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