# Epigenetic mechanisms in heroin seeking behavior

> **NIH NIH F32** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2020 · $32,655

## Abstract

PROJECT SUMMARY
Opioid abuse is an expanding national health epidemic. A central feature of addiction to opioids such as heroin,
is the high incidence of relapse to drug use despite available treatments. Underlying this propensity to relapse
are persistent neuroadaptations that emerge and develop during the course of drug use. The most profound of
these adaptations occur within brain regions associated with mediation of reward and motivation. The nucleus
accumbens (NAc) region is involved in the facilitation of drug reward, subsequent drug craving, and relapse to
drug use. This region undergoes extensive drug-induced dysregulation, in part mediated by epigenetic
mechanisms. Histone deacetylases (HDACs) are enzymatic regulators that can produce experience-dependent
alterations in transcription and translation. Class II HDACs, including HDAC5, are dysregulated by drugs of
abuse in the NAc and overexpression of HDAC5 can limit drug reward and drug-seeking behavior. When HDAC5
is localized to the nucleus, it is able to repress the transcription of many genes known to play an active role in
the suppression of drug-seeking behavior. However, the crucial time-point at which HDAC5 is acting to suppress
these behaviors, as well as the cell populations in which HDAC5 regulation is necessary are unknown.
Furthermore, candidate differentially regulated genes that HDAC5 may be acting on to suppress heroin-seeking
behaviors have not been investigated in in vivo drug self-administration models. The aims laid out in this proposal
will identify when HDAC5 is acting, where within the NAc HDAC5’s effects are necessary, and how HDAC5 may
be effecting the epigenetic landscape to limit heroin-seeking. These experiments employ a fusion of
breakthrough transgenic lines with leading-edge viral vector constructs and modern next generation sequencing
techniques. All analyses will be performed in a mouse model of the benchmark standard for substance abuse
research: drug self-administration. The Medical University of South Carolina is a leading center in the substance
abuse field and is an ideal location for the actuation of these experiments. The comprehensive experimental
design of these studies and rigorous application of pioneering techniques will significantly address the gap in
understanding of HDAC5’s ability to limit drug reward and provide significant learning and development
opportunities that will serve as a career-building foundation.

## Key facts

- **NIH application ID:** 9950843
- **Project number:** 5F32DA047845-02
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Sarah Margaret Barry
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $32,655
- **Award type:** 5
- **Project period:** 2019-07-01 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9950843

## Citation

> US National Institutes of Health, RePORTER application 9950843, Epigenetic mechanisms in heroin seeking behavior (5F32DA047845-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9950843. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*