# Traumatic stress and binge drinking as risk factors for excessive alcohol intake

> **NIH VA I01** · PORTLAND VA MEDICAL CENTER · 2021 · —

## Abstract

Post-traumatic stress disorder (PTSD) is classified as a trauma- or stressor-related disorder, and evidence
confirms an association between PTSD and the development of an alcohol use disorder (AUD). Despite
heterogeneity in the incidence of PTSD, high comorbidity of PTSD and AUD are reported in the veteran
population. Furthermore, the exacerbation of symptoms in veterans with comorbid PTSD/AUD negatively
influences recovery prognosis and effective therapeutic strategies. We and others found that exposure to
predator odor stress (PS), used as an animal model of PTSD, significantly increases anxiety-related behaviors
and subsequent alcohol (ethanol) intake in rodents. Most importantly, we observed heterogeneity in these
behavioral responses, as is observed in human PTSD/AUD patients. Additionally, prior binge drinking (BD)
produced a greater enhancement in ethanol drinking following intermittent PS in stress “sensitive” mice.
Specifically, “PS-sensitive” male and female C57BL/6J (B6) mice exhibited > 70% increase in ethanol intake (>
2.5 g/kg over baseline), while ethanol intake was unchanged in “resilient” mice. Additional studies in B6 mice
determined that BD alone produced sexually divergent changes in signaling pathways in the nucleus
accumbens (NAC), while the enhanced ethanol intake following BD and PS produced sex differences in
proteins related to the stress axis and neurosteroid synthesis in prefrontal cortex and hippocampus (NAC not
examined in that study). In conjunction with evidence for separate behavioral and epigenetic adaptations
underlying stress “sensitivity” and “resilience”, we hypothesize that: (1) distinct behavioral and molecular
adaptations confer “sensitivity” and “resilience” to the enhancing effect of BD and PS on later ethanol
drinking, (2) BD induces DNA methylation (DNAm) signals and associated changes in gene
expression that alter adaptability to PS, and (3) sex differences exist in the underlying mechanisms
in B6 mice. Aim 1 studies will determine whether “sensitivity” vs “resilience” to PS-enhanced drinking after
prior BD is associated with altered anxiety-related behavior, heart rate (HR), and/or ethanol reward and
whether sex differences exist in these relationships. Four groups will be tested: Group 1 (BD+4 weeks 23 h
ethanol drinking with intermittent PS; divided into “sensitive” and “resilient” subgroups); Group 2
(intermittent PS only); Group 3 (naïve); Group 4 (BD only). After the post-PS drinking (Group 1), final PS
(Group 2), or equivalent time point (Groups 3 & 4), HR and anxiety-related behavior will be assessed in one
study and conditioned place preference will be tested in a separate study. Aim 2 will identify epigenetic signals
and linked gene expression profiles in the NAC that confer “sensitivity” and “resilience” to PS-enhanced
drinking after prior BD. Groups will be as in Aim 1, but mice will be euthanized following final BD, post-PS
drinking, or final PS. We predict that the genome-wide DNAm analy...

## Key facts

- **NIH application ID:** 10074138
- **Project number:** 5I01BX002966-06
- **Recipient organization:** PORTLAND VA MEDICAL CENTER
- **Principal Investigator:** DEBORAH A. FINN
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2015-07-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10074138

## Citation

> US National Institutes of Health, RePORTER application 10074138, Traumatic stress and binge drinking as risk factors for excessive alcohol intake (5I01BX002966-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10074138. Licensed CC0.

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