# 8/11 Targeting Anti-inflammatory Gene Expression in Binge-like Drinking

> **NIH NIH U01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $377,237

## Abstract

Project Summary
High Drinking in the Dark (HDID) mice have been selectively bred to drink to intoxication. HDID mice are
genetically distinct and represent a unique genotype for drug screening. Many of the compounds that reduce
drinking in other strains (e.g., C57BL/6J) do not reduce drinking in HDID mice, and also fail to reduce drinking
in humans. Many INIA-Neuroimmune studies have found that alcohol alters inflammatory signaling. We
employed a rigorous approach for testing whether several compounds targeting immune signaling could
reduce binge-like drinking in HDID mice. To date, 14 out of 28 compounds tested in HDID mice were able to
reduce binge-like drinking in HDID mice. Apremilast, a phosphodiesterase type 4 inhibitor and our most
promising clinical target, and other compounds that reduced binge-like drinking have one thing in common -
they increase anti-inflammatory (e.g. IL-10) signaling. These results offer a broadly unifying hypothesis for
more mechanistic experiments to investigate how the balance of pro- and anti-inflammatory signaling regulates
binge-like drinking in HDID mice. Here, we study this mechanism in the context of initiation of binge-like
drinking, and determine whether this framework holds true under chronic binge drinking conditions. An
overarching goal of this proposal is to identify and target anti-inflammatory signatures to reduce drinking and
restore alcohol-induced changes in anti- and pro-inflammatory signaling in the brain. Specfic Aim 1 tests
whether specific inflammatory signaling pathways contribute to binge-like drinking in iHDID mice using a
combination of complementary molecular, genetic, pharmacological, and behavioral approaches in
collaboration with INIA-N PIs Roberto, Mangieri, Bilbo, and Lasek. Specific Aim 2 tests whether chronic binge-
like drinking is accompanied and/or regulated by anti-inflammatory gene expression in iHDID-1 mice. Aim 2 will
employ informatics approaches to identify compounds for behavioral and molecular studies in collaboration
with INIA-N PI Mayfield. This project also collaborates with INIA-Stress PIs Vazey/Mooreman and
Becker/Lopez to test the effects of promising compounds on other behaviors, and shares the HDID and HS/Npt
mouse lines as unique resources developed and maintained under this award with investigators nationwide.

## Key facts

- **NIH application ID:** 10771256
- **Project number:** 5U01AA013519-23
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Angela Renee Ozburn
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $377,237
- **Award type:** 5
- **Project period:** 2001-09-27 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10771256

## Citation

> US National Institutes of Health, RePORTER application 10771256, 8/11 Targeting Anti-inflammatory Gene Expression in Binge-like Drinking (5U01AA013519-23). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10771256. Licensed CC0.

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