# Delineating cell-specific transcriptomics associated with opioid craving in the nucleus accumbens

> **NIH NIH F32** · TEMPLE UNIV OF THE COMMONWEALTH · 2021 · $66,390

## Abstract

Project Summary
Opioid use has reached epidemic levels in the United States, and despite decades of research, very few
effective treatment options are available. In both humans and rodents, a counter-intuitive increase in craving in
response to drug-associated cues is observed following extended periods of abstinence, a phenomenon
known as incubation of craving. This craving is thought to contribute to the high rate of relapse observed in
patients with substance use disorder. Understanding the molecular mechanisms that drive incubation of
craving will be vital for the development of new effective therapeutics. Neurons that express dopamine D1
(D1+) or D2 (D2+) receptors define distinct cellular populations, which are thought to play divergent roles in
reward-related behaviors. Pharmacological inhibition of D1+ but not D2+ receptors in the nucleus accumbens
shell (NAcSh) blocks incubation of morphine craving, highlighting D1+ NAcSh cells as critical drivers of
incubation. D1+ and D2+ cells undergo differential synaptic plasticity in response to drugs of abuse, but how
these cell types are differentially influenced by incubation of morphine craving remains an important
unaddressed question. Additionally, in both humans and rodents, sex differences are observed in substance
use and abuse; females escalate to substance abuse faster and are at greater risk of relapse than men. These
sex differences can be further modified by estrous cycle in females, where periods of high estrogen during
estrus enhance incubation of cocaine craving. However, the role of estrous cycle in incubation of morphine
craving and the associated changes in gene expression remain unknown. Preliminary RNA-sequencing data in
the NAcSh of rats following 1 or 30 days of forced abstinence from morphine or saline intravenous self-
administration revealed that expression of the transcription factor Nr4a1, as well as several of its putative
target genes, is upregulated following 30 days of abstinence in males but not females. However, how estrous
cycle might impact Nr4a1 expression during incubation of craving remains unknown. Thus, this project will
investigate the cell-type specific role of Nr4a1 during incubation of morphine craving in male and female rats.
My central hypothesis is that Nr4a1 in D1+ NAcSh cells leads to incubation of morphine craving, and that this
will be enhanced during estrus in females. I will test this hypothesis by leveraging new technology to identify
cell-type specific changes in gene expression and by tracking the female estrous cycle. The training plan
outlined in this proposal will provide me the resources, skills and environment needed to complete this project
and to pursue an independent academic research career. Successful completion of these aims will provide a
greater understanding of the cell-type specific mechanisms underlying incubation of craving and will provide
support for a potential therapeutic target to prevent relapse.

## Key facts

- **NIH application ID:** 10139215
- **Project number:** 1F32DA052128-01A1
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Charlotte Chloe Bavley
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $66,390
- **Award type:** 1
- **Project period:** 2021-04-28 → 2022-04-27

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10139215

## Citation

> US National Institutes of Health, RePORTER application 10139215, Delineating cell-specific transcriptomics associated with opioid craving in the nucleus accumbens (1F32DA052128-01A1). Retrieved via AI Analytics 2026-06-23 from https://api.ai-analytics.org/grant/nih/10139215. Licensed CC0.

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