# Developing rodent models of PTSD/AUD: leveraging clinic-based strategies

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $249,579

## Abstract

RFA-AA-17-016 states that “Studies examining alcohol related behaviors in current models of PTSD and
potentially in novel animal models of PTSD are sought”. Animal models of PTSD are on the cutting edge of
exploiting individual differences to understand mechanisms underlying resilience and susceptibility to
psychopathology. Validated models of PTSD recapitulate the prevalence of PTSD in trauma-exposed
individuals (~15-30% depending on trauma). We will use 2 well-validated animal models of PTSD, social
defeat stress and predator stress, to understand in what biological contexts trauma and subsequent enduring
stress response provokes drinking behavior. Predator stress models the enduring effects of a severe single
traumatic event while social defeat stress models effects of chronic physical and emotional stress. Both
models produce variance in enduring response rates to trauma exposure, (30-50% of animals exhibit
prolonged behavioral and neurobiological change), providing etiological validity for PTSD. We propose to
examine if two highly translatable markers of trauma-symptom development, sleep disturbance and increased
peripheral immune signaling, predict development and/or maintenance of drinking after stress in rodents. This
approach addresses the RFA mandate to “identify biomarkers that will predict transition of PTSD to comorbid
PTSD-alcohol misuse.” The goal is to (1) develop robust cross-species biomarkers of long term-trauma effects
associated with increased alcohol consumption and (2) identify biomarkers that are predictive for treatment
response. We will test the hypothesis that sleep and inflammation abnormalities after trauma predict increased
drinking and treatment response. To test this hypothesis we will use a large (N=200/model) prospective,
longitudinal design based on clinical research approaches. This strategy enables use of sophisticated
statistical models to identify biological predictors of drinking behavior. We will assess clinical relevance by
comparing these findings to humans by leveraging our clinical database of a prospective, longitudinal study of
trauma in active duty service members (N=2600). This database includes data on trauma, PTSD symptoms,
alcohol dependence, sleep and peripheral inflammation both before and after a combat deployment. Once
validated, sleep and immune biomarkers identified in our animal models and validated in humans can be used
to screen for prophylactic and therapeutic treatment effects of novel pharmacotherapies.

## Key facts

- **NIH application ID:** 10237235
- **Project number:** 5R01AA026560-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** ANDRE DER-AVAKIAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $249,579
- **Award type:** 5
- **Project period:** 2017-09-12 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10237235

## Citation

> US National Institutes of Health, RePORTER application 10237235, Developing rodent models of PTSD/AUD: leveraging clinic-based strategies (5R01AA026560-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10237235. Licensed CC0.

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