# Dopamine D3 Receptors as a Potential Therapeutic Target for Heroin Abuse

> **NIH NIH F31** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2021 · $43,358

## Abstract

PROJECT SUMMARY
The opioid epidemic in the United States has reached unprecedented levels, and new treatments for opioid
and heroin addiction are desperately needed. Heroin abuse is traditionally treated with opioid replacement
therapies like methadone. However, these medications have negative side effects such as abuse liability and
respiratory depression, suggesting the need for novel, safe pharmacotherapeutic medications to treat opioid
use disorder. There is recent evidence that heroin produces its rewarding and addictive effects at least partially
through activation of the mesolimbic dopamine system, and that heroin seeking and intake in preclinical
addiction models can be modulated by treatments that target dopamine receptors. Specifically, dopamine D3
receptors have received considerable attention, as studies have shown D3 receptor antagonists reduce cue-
induced reinstatement, a model of relapse-like behavior, for nicotine, alcohol, cocaine, and opioids. These
findings suggest that D3 receptors may be a potential target for pharmacotherapies to treat heroin abuse and
that D3 receptor antagonists may decrease relapse vulnerability. Therefore, this study aims to investigate (1) if
acute and/or chronic administration of D3 receptor specific antagonists can decrease cue-induced heroin
reinstatement in male and female rats and (2) if D3 receptor alterations after chronic exposure to heroin and/or
extinction are driving relapse vulnerability. Because previous studies have shown that D3 receptor antagonists
have therapeutic efficacy after acute administration, in Specific Aim 1 we will determine if chronic
administration of a D3 antagonist is more effective than acute administration and if male and female rats
demonstrate decreased reinstatement responding after D3 receptor antagonist administration. Our preliminary
data suggest that D3 autoreceptors in the nucleus accumbens are overactive after chronic heroin exposure.
Therefore, in Specific Aim 2, we will determine if this increase in D3 receptor activity is maintained throughout
extinction and if females show the same alterations. Collectively, the proposed studies will provide insight into
the potential for D3 receptor antagonists to decrease relapse vulnerability as well as examine a potential
receptor target for future pharmacotherapeutic development. Further, the proposed studies will provide training
in behavioral and neurochemical assays as well as data analysis, interpretation, and dissemination through
manuscripts and presentations, which will serve as career development opportunities for the applicant.

## Key facts

- **NIH application ID:** 10220928
- **Project number:** 5F31DA049504-03
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Brianna Elyse George
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $43,358
- **Award type:** 5
- **Project period:** 2019-08-08 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10220928

## Citation

> US National Institutes of Health, RePORTER application 10220928, Dopamine D3 Receptors as a Potential Therapeutic Target for Heroin Abuse (5F31DA049504-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10220928. Licensed CC0.

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