# Sensitivity and resilience to increased alcohol drinking in males and females following traumatic stress

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $372,975

## Abstract

Project Summary
Post-traumatic stress disorder (PTSD) is twice as prevalent in females as in males, with a proportion of
individuals also developing an alcohol use disorder (AUD). Using predator odor stress (PS) as an animal
model of PTSD, we determined that two PS exposures significantly increased anxiety-related behavior and
neuronal activation in the hippocampus (HC) of male and female C57BL/6J (B6) mice. Notably, intermittent PS
significantly increased alcohol (ethanol) intake by 60% (males) and 71% (females), with heterogeneity in the
response. Further, “sensitivity” to PS-enhanced ethanol intake conferred significantly greater corticotropin
releasing factor receptor-1 (CRFR1) protein levels in female versus male HC, consistent with evidence for sex
differences in CRFR1 signaling following stress. The proposed studies build on the above evidence by testing
the hypothesis that comorbidity of PTSD and AUD is due to increased CRFR1 expression in HC
neurons projecting to mPFC and that sex differences in CRFR1 induction by PS contribute to this
comorbidity. Aim 1 will determine whether sex differences exist in the association between PS-enhanced
ethanol drinking and alteration in anxiety, heart rate (HR), and/or compulsive ethanol drinking in B6 mice. We
predict that PS-enhanced drinking in “sensitive” mice will be associated with an increase in anxiety, HR, and
compulsive drinking and that there will be sex differences in the pattern of changes. Aim 2 will map changes in
CRFR1 expression and neuronal activation by PS and by PS-enhanced drinking in crfr1-gfp mice. We predict
that there will be sex differences in brain regional CRFR1-colabelled activity patterns in response to
intermittent PS and in the relationship with ethanol intake. Aim 3 will manipulate the activity of CRFR1-
expressing neurons using chemogenetic or pharmacologic approaches and determine the impact on PS-
enhanced drinking. Two studies will use Designer Receptors Exclusively Activated by Designer Drugs
(DREADDs) in crfr1-cre mice to test the necessity and sufficiency of CRFR1 in ventral CA1, with inhibitory (Gi)
and excitatory (Gq) DREADDs, respectively. We predict that preventing PS-induced activation of ventral CA1
(Gi DREADD) will block PS-enhanced drinking only in “sensitive” mice, whereas activating the ventral CA1 (Gq
DREADD) will enhance ethanol intake in mice drinking ethanol without intermittent PS. A complementary study
will determine whether systemic administration of a CRFR1 antagonist will reduce PS-enhanced drinking
intake in B6 mice, with the prediction that the antagonist will be most effective in “sensitive” mice. Aim 4 will
determine whether manipulation of the projection from ventral CA1 to mPFC is important for PS-enhanced
drinking in B6 mice, by injecting Gi DREADDs into ventral CA1 and clozapine-N-oxide into mPFC. We predict
that preventing PS-induced activation of the ventral CA1 to mPFC projection will block PS-enhanced drinking.
Collectively, the info...

## Key facts

- **NIH application ID:** 10226335
- **Project number:** 5R01AA028680-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** DEBORAH A. FINN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $372,975
- **Award type:** 5
- **Project period:** 2020-08-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10226335

## Citation

> US National Institutes of Health, RePORTER application 10226335, Sensitivity and resilience to increased alcohol drinking in males and females following traumatic stress (5R01AA028680-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10226335. Licensed CC0.

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