# Pharmacology and Neurobiology of Binge Drinking: HDID Mice

> **NIH NIH U01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $432,843

## Abstract

Project Summary/Abstract
In the initial 5 years of INIA-Neuroimmune funding, we developed a novel assay for binge-like drinking, where
mice are offered limited access to 20% ethanol (EtOH) in water early during their circadian dark period. The
Drinking in the Dark (DID) assay has been widely adopted and used to probe mechanisms of binge-like
drinking. During the ensuing 10 years, we selectively bred two lines of mice for High Drinking in the Dark
(HDID-1 and HDID-2), by mating individuals reaching the highest blood alcohol levels (BALs) after a second
daily DID session. HDID mice achieve BALs between 170 and 150 mg% after 32 (HDID-1) and 25 (HDID-2)
selected generations, respectively. Binge-like drinking is a strong predictor of alcohol use disorder diagnosis
and has deleterious health consequences. These models represent genetic risk for high binge drinking. Binge-
like drinking has to date been used only infrequently to screen candidate drugs. Recent studies suggest that
HDID mice respond to treatment with some, but not all drugs known to reduce drinking (e.g., acamprosate but
not naltrexone). Because HDID mice appear to represent a selective model for screening, we propose to use
them to nominate and then test INIA-N targets. In Specific Aim 1, we will collaborate with INIA-N PIs Drs.
Mayfield, Ponomarev, and Farris to test novel neuroimmune-related targets suggested by their bioinformatics
analyses and rigorously test their efficacy in HDID mice. The Mayfield group will compare expression profiles
between HDID mice and their non-selected HS/Npt control line with data from the Library of Integrated
Network-based Cellular Signatures (LINCS), which comprises gene expression response profiles to >1000
perturbagens in multiple cell lines, including responses to many FDA-approved compounds. We hypothesize
that comparing the HDID vs HS gene expression differences with perturbagen-generated difference in LINCS
and seeking novel drugs that normalize HDID expression differences from HS will successfully predict drug
efficacy to reduce binge-like drinking. Preliminary testing has been carried out successfully for two targets
(phosphodiesterase type 4 inhibitor and Bruton's tyrosine kinase inhibitor). For drugs passing these screens,
our Specific Aim 2 will extend our efficacy tests of successful drugs to reduction of stress-induced escalations
of post-dependence drinking. Through this collaborative Specific Aim with INIA-Stress PIs Drs. Becker and
Lopez, we will test the reproducibility and generalization of drug effects in another drinking model, genotype
and laboratory. In Specific Aim 3, we will identify the brain localization of novel drug effects and determine their
cell type specificity using viral mediated RNAi in collaboration with INIA-N PI Dr. Lasek. We predict that some
neuroimmune targets will show neuronal specificity while others will selectively target glial cells. Aim 3 will also
measure the drug's physiological effects through collabora...

## Key facts

- **NIH application ID:** 9853694
- **Project number:** 5U01AA013519-19
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Angela Renee Ozburn
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $432,843
- **Award type:** 5
- **Project period:** 2001-09-27 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853694

## Citation

> US National Institutes of Health, RePORTER application 9853694, Pharmacology and Neurobiology of Binge Drinking: HDID Mice (5U01AA013519-19). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9853694. Licensed CC0.

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