# Contribution of locus coeruleus-derived galanin to opioid reward and reinforcement

> **NIH NIH R01** · EMORY UNIVERSITY · 2024 · $463,811

## Abstract

Project Summary
The opioid epidemic has been declared a national public health emergency. Current treatments have abuse
liability, target acute overdose only, and/or are ineffective for many people suffering from opioid addiction, and
new therapies are desperately needed. One promising target is the brain galanin system; reducing galanin
levels exacerbates morphine reward and withdrawal, while increasing galanin opposes opioid addiction-like
behaviors. However, the neuroanatomical source and target of this protective galanin have not been identified,
and the effects of galanin on voluntary opioid intake have not been investigated. The locus coeruleus (LC)
modulates the activity of the mesolimbic reward pathway and has been implicated in opioid addiction, and
80% of noradrenergic neurons in this nucleus co-express galanin. We have assembled a set of genetically
altered mice that either lack or overexpress galanin specifically in noradrenergic neurons to test the hypothesis
that LC-derived galanin suppresses the ability of opioids to disinhibit dopamine (DA) neurons in the ventral
tegmental area (VTA) and attenuates opioid reward/reinforcement, as well as acts in an autocrine manner to
prevent LC hyperactivity and reduces withdrawal symptoms. In Aim 1, we will use in situ hybridization to
determine the neurochemical identity of galanin receptor-expressing cells in the VTA, and slice and in vivo
electrophysiology to investigate the circuitry and cellular mechanisms underlying the ability of galanin to
oppose opioid-induced VTA DA neuron activity. In Aim 2, we will use the transgenic mice described above to
test the hypothesis that LC-derived galanin inhibits opioid reinforcement using an operant i.v. opioid self-
administration paradigm. In Aim 3, we will assess the ability of galanin to suppress LC hyperactivity, cellular
plasticity, and aversive symptoms during opioid withdrawal. Completion of these aims will lay the groundwork
for LC/galanin-based therapies for opioid addiction.

## Key facts

- **NIH application ID:** 10886527
- **Project number:** 5R01DA049257-05
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** DAVID WEINSHENKER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $463,811
- **Award type:** 5
- **Project period:** 2020-09-30 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10886527

## Citation

> US National Institutes of Health, RePORTER application 10886527, Contribution of locus coeruleus-derived galanin to opioid reward and reinforcement (5R01DA049257-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10886527. Licensed CC0.

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