# Opposing Contributions of Oxytocin and Corticotropin-Release Factor to Alcohol Dependence

> **NIH NIH R00** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2021 · $249,000

## Abstract

Project Summary
Alcohol use disorder is a global public health issue for which more effective treatments are
urgently needed. Alcohol dependence is characterized by exacerbated brain stress signaling
that drives compulsive drinking. A major component of this signaling is the pro-stress
neuropeptide corticotropin releasing factor (CRF). Oxytocin is a neuropeptide with an anti-
stress, anti-CRF profile of action, which blocks compulsive drinking in alcohol-dependent rats.
However, the neuronal circuitry through which oxytocin exerts its anti-compulsive drinking effect
is not known. Therefore, the aim of the present Pathway to Independence Award proposal is to
obtain the necessary training to identify, interrogate, and manipulate mechanisms underlying
oxytocin’s ability to block compulsive alcohol drinking. Technical training will be conducted at
the National Institute on Drug Abuse, Intramural Research Program and prepare the candidate
to use these techniques independently in the proposed and future experiments. Training will be
complimented with mentorship and career development activities tailored toward the candidate’s
goal of securing a tenure-track academic position at an extramural research institute.
 Oxytocin fibers project from the hypothalamus to allow local release of oxytocin in sites
throughout the brain, including the extended amygdala, a collection of brain nuclei in which CRF
mediates dysregulated stress signaling in alcohol dependence. This proposal will first aim to
map oxytocin projections throughout the whole brain, and identify CRF cells and their co-
expression with the oxytocin receptor in terminal regions. The synaptic interaction between
oxytocin fibers and CRF cells will be determined using immuno-electron microscopy. This will
allow the identification of regions with high likelihood of oxytocin-CRF interaction. The second
aim is to use fiber photometry to monitor the activity of CRF cells in awake-behaving CRF-Cre
rats, in regions of likely oxytocin-CRF interaction. This will allow in vivo assessment of CRF cell
function in alcohol dependence, as well as in response to alcohol drinking and oxytocin
administration. The third aim is to use optogenetics to activate or inhibit the release of oxytocin
from terminal fibers in regions of likely oxytocin-CRF interaction. This will allow determination of
a causal role of local oxytocin action in alcohol drinking and other behaviors dysregulated in
alcohol dependence (anxiety and pain). Completion of these studies will provide novel insights
into the neurocircuitry and interaction of oxytocin and CRF, which have opposing roles in
alcohol dependence. The present project is of high importance for public health, given the
potentially high therapeutic value of oxytocin-based medications for alcoholism.

## Key facts

- **NIH application ID:** 10414323
- **Project number:** 4R00DA048530-02
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Brendan Tunstall
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2021-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10414323

## Citation

> US National Institutes of Health, RePORTER application 10414323, Opposing Contributions of Oxytocin and Corticotropin-Release Factor to Alcohol Dependence (4R00DA048530-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10414323. Licensed CC0.

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