# Hypothalamic oxytocin influence on extended amygdala CRF neurons in alcohol dependence

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

## Abstract

PROJECT SUMMARY/ABSTRACT
Alcoholism is a chronic relapsing disorder characterized by compulsive seeking and consumption of alcohol, the
result of a transition from recreational use to abuse and dependence. Most alcoholics do not receive treatment,
and current medications do not work for all sufferers, highlighting the need for new therapeutics. Alcohol
dependence induces heightened activity of brain stress systems, resulting in the negative affective state
associated with withdrawal. The neuropeptide oxytocin (OT) is anti-stress, and systemic administration of OT
decreases withdrawal symptom severity and drinking in alcoholics. The central amygdala (CeA) and bed nucleus
of the stria terminalis (BNST) are two brain regions considered to be hubs for stress processing, and the role of
pro- and anti-stress neuropeptides in these brain regions are critical for the development of alcohol dependence.
Synaptic activity in the CeA and BNST is sensitive to acute alcohol, and plays a critical role in the behavioral
effects of ethanol consumption. The CeA and BNST are rich in neuropeptides and their receptors, including
corticotropin releasing factor (CRF) and OT, and ethanol’s effects on synaptic signaling in these regions may be
modulated by neuropeptide activity. CRF is involved in the heightened stress and anxiety associated with alcohol
dependence and withdrawal, and blocking CRF activity in the CeA and BNST can reduce alcohol drinking. Thus,
the balance between anti- and pro-stress signaling is likely perturbed during the transition to alcohol dependence,
characterized by an overactive CRF system. OT producing neurons in the paraventricular and supraoptic nuclei
of the hypothalamus project to both the CeA and BNST, to specific subdivisions that contain CRF neurons. Thus,
OT may act directly on CRF neurons of the CeA and BNST to decrease withdrawal severity and alcohol drinking.
This project will characterize hypothalamic OT neuronal input to CRF neurons of the CeA and BNST, whether
these circuits are disrupted by alcohol dependence, and involvement of these circuits in alcohol dependence
induced drinking. Viral vector mediated expression of fluorescent markers and Designer Receptors Exclusively
Activated by Designer Drugs (DREADDs) will allow for electrophysiological and molecular characterization of
OT circuits in the CeA and BNST, and behavioral testing of OT circuit involvement in alcohol dependence
induced alcohol drinking. Experimental studies will begin during the K99 phase, and will be completed during the
R00 phase at a new institution in the principal investigator’s (PI) independent laboratory. Towards this career
goal, during the K99 phase, the PI will train under the mentorship team in new techniques including the use of
viral vector based protein expression and synaptic tracing, immunohistochemistry, in situ hybridization, and
behavioral pharmacology to complement the PI’s experience with electrophysiology. During the R00 phase, the
mentors...

## Key facts

- **NIH application ID:** 10489454
- **Project number:** 4R00AA026638-03
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Dean Kirson
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2018-09-20 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10489454

## Citation

> US National Institutes of Health, RePORTER application 10489454, Hypothalamic oxytocin influence on extended amygdala CRF neurons in alcohol dependence (4R00AA026638-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10489454. Licensed CC0.

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