# Olfactory targets of alcohol use disorder medications

> **NIH NIH R21** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $221,375

## Abstract

Project Summary
Alcohol use disorder (AUD) is a severe public health problem. Limited FDA-approved pharmacotherapies exist
for AUD, and their efficacy is often insufficient. Therefore, development of new approaches for AUD treatment
is necessary. A large number of preclinical studies showed that administration of oxytocin (OXT) decreases
alcohol consumption in rodents. In clinical studies, intranasally administered (IN) OXT can also decrease
alcohol craving, alcohol cue reactivity and measures of heavy alcohol drinking. However, some recent studies
have reported lack of OXT's effects on measures of excessive alcohol drinking indicating the need for
developing more nuanced treatment approaches. Understanding mechanisms underlying OXT's effect on
alcohol intake may help the development of such approaches. IN-administered labelled OXT in non-human
primates was distributed along the olfactory and trigeminal nerves. Therefore, exogenously administered OXT
is likely to act along this route, with its potential first stage of actions in the anterior olfactory areas. Indeed, the
anterior olfactory nucleus (AON) and the main olfactory bulb (MOB) express high levels of OXT receptor
(OXTR) and the vasopressin receptor 1a (AVPR1a), respectively. We hypothesize, therefore, that activation of
these receptors in the anterior olfactory regions results in decreased alcohol consumption. The goal of this
exploratory project is to address this innovative hypothesis. This goal will be achieved in three specific aims. In
Aim 1, we will examine whether chemogenetic activation of OXTR-containing AON neurons can regulate
alcohol consumption in male and female mice. In Aim 2 we will examine whether chemogenetic activation of
AVPR1a-containing MOB neurons can regulate alcohol consumption in male and female mice. In Aim 3 we will
examine whether the anterior olfactory OXTR and AVPR1a contribute to OXT's inhibitory effects on alcohol
consumption in male and female mice through a region-selective conditional deletion of OXTR. Taken
together, these experiments will thoroughly test the role of anterior olfactory OXTR and AVPR1a in voluntary
alcohol drinking. On one hand, they will provide a background for a thorough investigation of mechanisms
involved in this role. On the other hand, they may provide a translational background for the potential of
targeting the olfactory systems in the treatment of AUD.

## Key facts

- **NIH application ID:** 10946292
- **Project number:** 1R21AA031708-01
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Andrey E Ryabinin
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $221,375
- **Award type:** 1
- **Project period:** 2024-09-26 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10946292

## Citation

> US National Institutes of Health, RePORTER application 10946292, Olfactory targets of alcohol use disorder medications (1R21AA031708-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10946292. Licensed CC0.

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