# Examining the modulatory role of galanin in opioid reward

> **NIH NIH F32** · EMORY UNIVERSITY · 2024 · $73,828

## Abstract

PROJECT SUMMARY
 The opioid epidemic in the United States has reached critical proportions, with opioid-related overdoses
contributing to more than 75% of drug overdose deaths. This crisis not only leads to significant mortality rates
but also poses a significant economic burden on society. Despite the prevalence of opioid use disorders (OUD),
the available treatment options remain limited, with only 3 FDA-approved medications, and there is a critical
need to develop novel therapeutics. One way to develop novel treatments is by examining endogenous factors
that modulate opioid responses such as galanin, a neuropeptide that is known to oppose opioid reward. Galanin
signals through three G-protein coupled receptors (GPCRs) including GalR1, which preferentially forms
heteromers with µ-opioid receptors (MOR) in the ventral tegmental area (VTA), a key node in the mesolimbic
reward system. Recent literature indicates that galanin blocks MOR-mediated dopamine release in the VTA via
GalR1-MOR heteromer interactions. Recently, our lab found that intra-VTA galanin administration attenuates
morphine conditioned place preference (CPP) in male and female mice, identifying a neuroanatomical substrate
for galanin action in opioid reward. However, the mechanisms underlying galanin’s ability to attenuate morphine
CPP are not clear. Thus, the proposed experiments were designed with 2 key goals: 1) identify the source of
endogenous galanin in the VTA that opposes opioid signaling, and 2) determine the role of the GalR1-MOR
heteromer in the VTA in opioid reward. The overarching hypothesis of this proposal is that galanin from the lateral
hypothalamus (LH) signals through GalR1-MOR heteromers on GABAergic projections from the rostromedial
tegmental nucleus (RMTg) within the VTA to oppose morphine CPP. A combination of behavioral, molecular,
pharmacological, and genetic tools will be used to test this hypothesis in male and female mice. In Aim 1, I will
use retrograde viral-assisted tracing and RNAscope in situ hybridization to determine all endogenous sources of
galanin to the VTA. Then, I will ablate galanin in the LH, which we know contains galaninergic projections to the
VTA and modulates opioid reward, by locally infusing Cre-expressing virus into the LH of floxed galanin
conditional knockout mice and quantify the density of the galanin-positive fibers in the VTA. Additionally,
morphine CPP will determine the consequences of removing LH galanin inputs to the VTA on opioid reward. In
Aim 2, a validated GalR1-MOR heteromer interfering peptide will be co-infused with galanin into the VTA to
determine whether local heteromer signaling is necessary for galanin to attenuate morphine CPP. Conversely, a
novel viral construct will be used to overexpress GalR1 selectively in MOR-containing GABAergic neurons of the
RMTg. Together, these experiments will provide crucial information regarding the role of galanin in opioid reward
and have the potential to identify the GalR1-MO...

## Key facts

- **NIH application ID:** 10998115
- **Project number:** 1F32DA061631-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Brittany Sara Pate
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $73,828
- **Award type:** 1
- **Project period:** 2024-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10998115

## Citation

> US National Institutes of Health, RePORTER application 10998115, Examining the modulatory role of galanin in opioid reward (1F32DA061631-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10998115. Licensed CC0.

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