# Circular RNA signaling in opioid seeking phenotypes

> **NIH NIH DP1** · TEMPLE UNIV OF THE COMMONWEALTH · 2022 · $475,500

## Abstract

Abstract:
Substance use disorder is a costly and debilitating chronic disorder, characterized by high rates of relapse
despite successful attempts at rehabilitation and periods of abstinence. In addition, the rates of overdose and
death associated with the opioid class of drugs have dramatically risen over the last decade and represent a
major public health burden. To identify putative drug targets for the treatment of opioid use disorder, the
molecular mechanisms that govern opioid seeking must be delineated. The goal of this proposal is to address
this critical barrier in the field of substance abuse research by exploring entirely new mechanisms that
modulate opioid seeking from a class of RNA called circular RNAs. Although circular RNAs have never been
studied in drug seeking behaviors, this species of RNA has the potential to broadly influence cellular signaling
at the epigenetic, transcriptional and translational levels, which in turn may impact a wide range of behavioral
phenotypes. Circular RNAs are single-stranded transcriptional splice products that result from backsplicing of
3' to 5' ends of mRNA. Such splice products are beginning to be explored in the brain, with some expressed at
higher levels than their mRNA counterparts, and have been reported to modulate critical processes including
microRNA activity, gene expression, protein translation and even cognitive behaviors. We have identified a set
of circular RNAs and their biogenesis enzymes that are regulated after heroin self-administration in the rat
orbitofrontal cortex (OFC), a brain region essential to reward seeking. During the award period, we will explore
the hypothesis that altered OFC circular RNA signaling contributes to opioid seeking phenotypes. We will use a
multi-disciplinary approach to examine the cellular and behavioral consequences of heroin-induced circular
RNA expression in a rat model of opioid seeking. First, heroin-associated circular RNAs will be genetically
manipulated in the OFC to determine their contribution to motivation for opioids and relapse to opioid seeking
after extinction or abstinence. We will then define the cellular phenotype of heroin-associated circular RNAs in
the OFC for insights into the cellular circuits that have altered circRNA biogenesis as a result of heroin
exposure. Finally, we will identify signaling pathways downstream of heroin-associated circular RNAs in the
OFC to describe the molecular interactions of this novel class of RNA within drug-exposed neurons. Our
dataset of heroin-associated circular RNAs have never been studied in the brain before and represent an
entirely new area of research in the field of substance abuse. Therefore, the outcome of the unprecedented
proposed studies will shed light on novel mechanisms that govern drug seeking and provide essential insight
into the neurobiology of substance abuse.

## Key facts

- **NIH application ID:** 10401902
- **Project number:** 5DP1DA051550-03
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Stephanie Daws
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $475,500
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401902

## Citation

> US National Institutes of Health, RePORTER application 10401902, Circular RNA signaling in opioid seeking phenotypes (5DP1DA051550-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10401902. Licensed CC0.

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