# Impact of stress on heroin seeking and ventral pallidal synapse function

> **NIH NIH F30** · UNIVERSITY OF COLORADO DENVER · 2023 · $38,977

## Abstract

PROJECT SUMMARY:
Deaths related to opioid use disorders (OUD) have sky-rocketed in recent years, leading to a widespread public
health crisis. This opioid endemic is worsened by a lack of effective therapeutic intervention strategies that
directly target or reverse the opioid induced neuroadaptations driving drug use and relapse. Prior research
indicates that experiencing a major stressful event in life is the greatest risk factor for exacerbated opioid use
and relapse among adults. Congruent with clinical data, preclinical work indicates that acute stress in adulthood
increases psychostimulant seeking in intravenous drug self-administration rodent models, but the effects of acute
stress on opioid seeking remain unknown. Further, the neurobiological mechanisms by which stress confers
OUD susceptibility are unclear. Emerging literature shows that ventral pallidal glutamate neurons (VPGlu) are key
regulators of drug seeking behavior and aversive states, which suggests that this neuronal subpopulation may
be a strong candidate for mediating the effects of stress on OUD-relevant circuit function that exacerbates OUD
pathology. My preliminary data sought to begin addressing these gaps in the OUD literature by examining how
acute stress impacts heroin sensitization and VPGlu activity using in vivo miniscope Ca2+ imaging in non-head
fixed male and female mice. To the best of my knowledge, this preliminary work represents the first in vivo
characterization of VPGlu activity during intense acute stress, and I am the first to report that VPGlu are responsive
to both stress and heroin. Furthermore, my sensitization data demonstrate that stress produces sexually
dimorphic changes in the psychomotor effects of heroin. Taken together, these preliminary data show that adult
acute stress alters the psychomotor properties of heroin and highlight VPGlu as promising mediators of stress and
OUD-relevant behaviors. My data warrant further investigation into the impact of stress on clinically relevant
opioid behaviors such as motivation and relapse to heroin seeking, and the systematic characterization of how
stress, opioids, and their intersection regulate the activity of VPGlu by altering synaptic inputs onto these cells.
Together, my preliminary data informed my main hypothesis that acute stress will enhance heroin
motivation and relapse to heroin seeking and that stress and opioids interact to alter VPGlu synaptic
function. The goals of this proposal are to interrogate 1) how stress impacts the motivation and relapse to heroin
seeking using an intravenous self-administration model and 2) assess the effect of stress, opioids, and their
interaction on synaptic function of VPGlu using ex vivo whole cell patch clamp electrophysiology. The outcomes
of this proposal will determine the consequences of acute stress on clinically relevant behavioral responses to
heroin and systematically characterize alterations in synaptic function of a newly established stress-reactive
n...

## Key facts

- **NIH application ID:** 10693872
- **Project number:** 5F30DA057053-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Carley N Miller
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $38,977
- **Award type:** 5
- **Project period:** 2022-08-03 → 2025-08-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10693872

## Citation

> US National Institutes of Health, RePORTER application 10693872, Impact of stress on heroin seeking and ventral pallidal synapse function (5F30DA057053-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10693872. Licensed CC0.

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