# 9/11 Neuroimmunophysiology of excessive alcohol intake

> **NIH NIH U01** · UNIVERSITY OF TEXAS AT AUSTIN · 2022 · $356,625

## Abstract

PROJECT SUMMARY/ABSTRACT
This Integrative Neuroscience Initiative on Alcoholism (INIA-Neuroimmune, INIA-N) consortium component is for
a U01 research project that seeks to determine how neuroimmune signaling molecules and glia contribute to
neuronal adaptations in the nucleus accumbens that promote excessive ethanol drinking. Prior work by this INIA-
N component identified neuronal adaptations in the nucleus accumbens (NAc) that are associated with excessive
alcohol consumption. In particular, we found that ethanol dependence and excessive intake are associated with
plasticity in glutamatergic synapses on dopamine D1 receptor-expressing medium spiny neurons (D1MSNs),
which comprise a major output pathway of the NAc that is heavily involved in reward-based behaviors. Recently
we discovered that, although synaptic excitation is enhanced, the membrane excitability of these neurons not
only is suppressed during acute withdrawal from ethanol, but is strongly, inversely, correlated with prior ethanol
intake. We will employ mouse behavioral models of chronic and excessive drinking, genetically engineered mice,
and brain slice electrophysiology to test the hypothesis that neuroimmune activity contributes to these synaptic
and membrane adaptations of D1MSNs. Specific aim 1 will evaluate how neuronal physiology is altered by the
cytokine interleukin-33 (IL-33) in an ethanol-dependent manner, and it will use genetically-engineered mice for
inducible and conditional deletion of IL-33, or its receptor, from specific cell types (microglia, astrocytes, and/or
neurons) to probe the role of this signaling pathway in the escalation of alcohol intake. Specific aim 2 will take a
broader approach, using brain slice electrophysiology to ask whether NAc microglia exhibit functional
adaptations that correlate with alcohol intake and its associated adaptations in D1MSNs. Specific aim 3 will be
collaborative studies on other neuroimmune signaling and regulatory molecules identified by INIA-N investigators’
as playing a role in excessive alcohol intake. Here we will again use brain slice electrophysiology and will
determine whether manipulations of these neuroimmune molecules may alter NAc D1MSN physiology to
regulate alcohol consumption. These studies will serve the mission of NIAAA by generating new, fundamental
knowledge about the effects of alcohol on brain health, and seeks to apply such knowledge to identify new
targets for the treatment of excessive alcohol consumption.

## Key facts

- **NIH application ID:** 10412292
- **Project number:** 2U01AA016651-16
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Regina A. Mangieri
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $356,625
- **Award type:** 2
- **Project period:** 2006-09-30 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10412292

## Citation

> US National Institutes of Health, RePORTER application 10412292, 9/11 Neuroimmunophysiology of excessive alcohol intake (2U01AA016651-16). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10412292. Licensed CC0.

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