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

> **NIH NIH K99** · SCRIPPS RESEARCH INSTITUTE, THE · 2020 · $105,300

## 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.
CeA and BNST synaptic activity are sensitive to acute alcohol and play a critical role in the behavioral effects of
ethanol consumption. The CeA and oval BNST are rich in corticotropin releasing factor (CRF) neurons, as well
as OT receptors, and acute OT modulates synaptic signaling in these regions in sex-specific ways. 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, but it is not yet known if OT exerts its effects
through action on CRF neurons. Thus, OT may act directly on CRF neurons of the CeA and BNST to decrease
withdrawal severity and alcohol drinking. The purpose of this project is to 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. OT effects on GABAergic transmission in
the CeA of naïve and alcohol dependent animals has been elucidated, finding sexually dimorphic effects of OT
and alcohol. Additionally, oxytocin receptor co-expression with CRF was high in the lateral CeA and independent
of sex or alcohol history, but alcohol dependence decreased OT expressing neurons in the paraventricular
nucleus of the hypothalamus (PVN), one major source of OT in the brain. The research progress of this project,
as well as the timely transition of the principal investigator (PI) to a position as head of an independent laboratory
at a new institution, has been directly negatively impacted by the COVID-19 pandemic and resulting hiring
freezes and shut down of research activities. The requested supplement and extension would allow the
completion of experiments investigating OT effects on CRF+ specific neurons of the CeA and BNST, as well as
completion of experiments characterizing the PVN(OT) -> CeA(CRF) and PVN(OT) -> BNST(CRF) pathways via
viral vector mediated expression of Designer Receptors Exclusively Activated by Designer Drugs (DREADDs).
The supplement and extension...

## Key facts

- **NIH application ID:** 10231694
- **Project number:** 3K99AA026638-02S1
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Dean Kirson
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $105,300
- **Award type:** 3
- **Project period:** 2018-09-20 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10231694

## Citation

> US National Institutes of Health, RePORTER application 10231694, Hypothalamic oxytocin influence on extended amygdala CRF neurons in alcohol dependence (3K99AA026638-02S1). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10231694. Licensed CC0.

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