# Role of nicotinic receptors in inhibitory GABA neurons on alcohol reward and behavior

> **NIH NIH F31** · UNIVERSITY OF MINNESOTA · 2020 · $40,496

## Abstract

PROJECT SUMMARY
Excessive consumption of alcohol contributes to 9.8% of preventable deaths annually, and alcohol abuse costs
$2.5 billion each year in healthcare and economic expenses. Despite the high costs of alcohol abuse,
consumption has increased significantly over the past decade. There are only 3 FDA-approved
pharmacotherapies to reduce alcohol use, all with low efficacy in achieving and maintaining abstinence,
highlighting the need for more effective treatments for alcohol abuse. One of the major barriers to developing
better treatments for alcohol abuse is the multitude of cellular and molecular mechanisms underlying alcohol
reward. Recent studies indicate the rewarding properties of alcohol are dependent upon its interaction with
nicotinic acetylcholine receptors (nAChRs) in reward pathways. nAChRs in the midbrain reward circuit
stimulate dopamine (DA) release, which mediates alcohol reward. The α4 subunit is of particular interest in
alcohol addiction, as pharmacotherapies targeting this subunit decrease alcohol consumption in human and
animal models. Additionally, α4 knockout mice show reduced alcohol consumption and DA release, and do not
reduce their alcohol consumption in response to nAChR drugs. α4 nAChRs are found within several cell types
in the ventral tegmental area (VTA), including DA projection neurons and local GABA neurons, which provide
inhibitory tone to DA neurons. Recent studies demonstrate that VTA GABA neurons are critical mediators of
reward behaviors, as activating these neurons disrupts sucrose consumption and conditions a place aversion.
Alcohol increases DA neuron firing frequency, which influences alcohol reward behavior. Alcohol also
modulates the activity of VTA GABA neurons, but the role of nAChRs in this process has not been studied.
Current approaches in the field cannot probe the role of α4 nAChRs in individual cell populations, and the
mechanism through which nAChRs on inhibitory GABA neurons modulate alcohol reward remains unknown.
To address this gap in knowledge, we have developed a conditional viral gene delivery strategy that initiates
knockdown of the α4 subunit selectively within VTA GABA neurons. The goal of this proposal is to define the
role of the α4 nAChR subunit in VTA GABA neurons in alcohol consumption and reward. We hypothesize that
nAChRs containing the α4 subunit in VTA GABA neurons decreases alcohol reward and consumption through
inhibition of DA neuron excitability. The specific aims of this project include: 1) determine the role of the α4
nAChR subunit in VTA GABA neurons in voluntary alcohol consumption in mice; and 2) determine the role of
the α4 nAChR subunit in VTA GABA neurons in the DA neuron-activating and subjective rewarding properties
of alcohol. This proposal will provide novel and important information about the role of the α4 nAChR subunit in
modulating alcohol reward. By identifying important cell types and nAChR subunits in alcohol reward, the
results of this study wil...

## Key facts

- **NIH application ID:** 9886068
- **Project number:** 5F31AA026782-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Janna K Moen
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $40,496
- **Award type:** 5
- **Project period:** 2019-03-01 → 2021-02-07

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9886068

## Citation

> US National Institutes of Health, RePORTER application 9886068, Role of nicotinic receptors in inhibitory GABA neurons on alcohol reward and behavior (5F31AA026782-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9886068. Licensed CC0.

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