# GABAB receptor-dependent signaling in alcohol consumption and reward

> **NIH NIH F31** · UNIVERSITY OF MINNESOTA · 2021 · $31,499

## Abstract

PROJECT SUMMARY
Over 16 million people in the United States are diagnosed with Alcohol use disorder (AUD) each year. AUD is
characterized by compulsive alcohol use, loss of control over intake, and negative emotional states during
periods of withdrawal. The long-term success of current treatment strategies for AUD is low, emphasizing the
need for new approaches to treat a broader patient population. The premise of my research is that by better
understanding the cellular and molecular mechanisms in the brain that regulate alcohol consumption and reward,
new or improved therapeutic strategies for treatment of AUD can be envisioned and developed. My project will
investigate the influence of an inhibitory G protein-dependent signaling pathway on alcohol consumption and
reward. Baclofen, a GABAB receptor (GABABR) agonist, decreases AUD-associated symptoms in preclinical and
clinical settings. In rodents, baclofen suppresses consumption and reward when administered either systemically
or directly to the ventral tegmental area (VTA), a key reward-related brain region. The output of VTA dopamine
(DA) neurons, the largest sub-population of neurons in the VTA, is moderated by inhibitory G protein-dependent
signaling pathways, including signaling mediated by GABABR. Additionally, different proteins, including
Regulator of G protein Signaling (RGS) proteins, act to modulate GABABR-dependent inhibition. The AIMS of
my project are to probe the impact of GABABR-dependent signaling in VTA DA neurons on alcohol-related
behavior (AIM 1), and to Identify the role of R7 RGS proteins in GABABR-dependent signaling in VTA DA neurons
(AIM 2). My working hypothesis is that GABABR-dependent signaling in VTA DA neurons suppresses alcohol
consumption and reward, and that this signaling pathway is subject to negative regulation by a specific subtype
of RGS protein, RGS6. I propose to test this hypothesis using CRISPR/Cas9-mediated gene ablation targeting
VTA DA neurons, in addition to ex vivo slice electrophysiology and behavioral analysis. Successful completion
of this proposal will improve our understanding of the role that GABABR-dependent signaling in VTA DA neurons
plays in alcohol consumption and reward, and reveal whether pharmacologic or genetic enhancement of this
inhibitory signaling pathway holds promise as a novel approach to treat aspects of AUD. Knowledge gained in
this effort will help inform the improvement of treatment and prevention of AUD.

## Key facts

- **NIH application ID:** 10231447
- **Project number:** 1F31AA028726-01A1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Margot Clara DeBaker
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $31,499
- **Award type:** 1
- **Project period:** 2021-05-24 → 2022-04-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10231447

## Citation

> US National Institutes of Health, RePORTER application 10231447, GABAB receptor-dependent signaling in alcohol consumption and reward (1F31AA028726-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10231447. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*