# Early-Life Stress Drives Increased Heroin Vulnerability: Role of D3 Receptors

> **NIH NIH F99** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2022 · $47,752

## Abstract

PROJECT SUMMARY
Stress and addiction are intricately linked neural processes. Acute stress can serve as a stimulus for relapse to
compulsive drug seeking following abstinence, and chronic stress can induce escalated drug intake to multiple
classes of drugs. The Jones lab and others have shown that the chronic psychosocial stressor of adolescent
social isolation (aSI) leads to impairments in dopamine (DA) function in the nucleus accumbens (NAc) and
increased vulnerability to stimulant drug and alcohol taking that persists into adulthood. However, it is unknown
how aSI affects consumption of opioids. In the current proposal, I have demonstrated that aSI leads to a robust
increase in heroin self-administration, propensity for relapse, and heroin withdrawal-induced negative affect.
This increase in vulnerability to heroin in aSI rats was coupled with data showing a greater reduction of
dopamine function than aGH animals that may drive this increase in heroin behaviors in aSI animals. The F99
phase of this proposal will primarily examine the role dopamine D3 autoreceptor (D3autoR) in the NAc in
driving increased heroin vulnerability and reduced dopamine transmission in aSI rats. I hypothesize that the
combination of aSI stress and heroin self-administration synergistically increase D3autoR-mediated
adaptations in the mesolimbic DA system producing hypodopaminergia and increasing heroin use vulnerability.
The proposed project will also help the candidate, Ms. Brianna George, achieve her career goal of becoming
an independent investigator at a research-intensive institution. This project provides training in valuable
research techniques, including fast-scan cyclic voltammetry, RNAscope, and gene silencing. Further, the
proposed studies will provide professional and technical training to prepare the candidate to successfully
transition to a postdoctoral position (K00) in a laboratory that studies the neural-circuitry driving vulnerability to
drug-seeking behavior. The complete plan proposed here for both the F99 and K00 phases has been designed
to develop an independent neurobiologist prepared for a transition to a successful postdoctoral position and,
ultimately, independent tenured investigator.

## Key facts

- **NIH application ID:** 10541392
- **Project number:** 1F99NS129177-01
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Brianna Elyse George
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $47,752
- **Award type:** 1
- **Project period:** 2022-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10541392

## Citation

> US National Institutes of Health, RePORTER application 10541392, Early-Life Stress Drives Increased Heroin Vulnerability: Role of D3 Receptors (1F99NS129177-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10541392. Licensed CC0.

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