# Alcohol and Traumatic Brain Injury; Neuronal and Behavioral Consequences

> **NIH NIH R01** · LSU HEALTH SCIENCES CENTER · 2020 · $328,500

## Abstract

Project Summary
Traumatic brain injury (TBI) afflicts many men and women in both military and civilian populations. The early
post-TBI period is characterized by neuroinflammation and oxidative stress followed by neurobehavioral changes
that include sleep disturbances, neuroendocrine dysfunction, cognitive impairments, and behavioral impairments
that include higher anxiety and depression, increased stress sensitivity, anhedonia, impulse control deficits, and
higher pain sensitivity. All of these behavioral symptoms can promote escalated alcohol drinking in humans in
an attempt to mitigate their symptoms, and this can eventually increase the likelihood of an alcohol use disorder
(AUD) diagnosis. The neurobiological mechanisms underlying post-TBI escalation of alcohol drinking are not
known. Critical from a healthcare burden perspective, our lab and others have shown that post-TBI alcohol
exposure impairs recovery of neurobehavioral function, exacerbates gliosis, and prevents resolution of
neuroinflammation. Preliminary data show increased glutamatergic signaling and synaptic hyperexcitability at
the site of injury and in the basolateral amygdala, which we believe underlies previously observed post-TBI
escalation of alcohol drinking and increased motivation to obtain alcohol. Moreover, our data show that a single
post-injury administration of JZL184, a monoacylglycerol lipase (MAGL) inhibitor that prevents endocannabinoid
degradation, attenuates neuroinflammation and improves neurobehavioral recovery post-TBI. In addition,
JZL184 rescues excessive glutamatergic signaling and neuronal hyperexcitability at site of injury, and reduces
motivation to obtain alcohol. Proposed studies will use male and female rats to test the hypothesis that synaptic
hyperexcitability is associated with post-TBI increases in anxiety-like behavior and alcohol drinking. We predict
that pharmacological (i.e., JZL184) and non-pharmacological (i.e., abstinence) therapeutic interventions will
reduce post-TBI escalation of alcohol drinking and prevent post-TBI synaptic hyperexcitability in alcohol drinkers.
Studies proposed will use an integrated experimental approach (behavior, immunohistochemistry, biochemistry,
electrophysiology, pharmacology, and chemogenetics). An interdisciplinary team of investigators with
established records of accomplishment on studies of TBI and inflammatory responses to alcohol (Molina); animal
models of alcohol self-administration, dependence, and behavioral pharmacology (Gilpin); biochemical signaling
mechanisms of alcohol dependence (Edwards); and electrophysiological investigations of neuronal synaptic
circuitry (Middleton) will conduct them. The overarching goal of this project is to determine whether preventing
pathological post-TBI synaptic plasticity in amygdala prevents post-TBI escalation of alcohol drinking and
improves post-TBI outcomes. Studies will be supported by the outstanding scientific environment and Core
analytical facilities supp...

## Key facts

- **NIH application ID:** 9904464
- **Project number:** 5R01AA025792-03
- **Recipient organization:** LSU HEALTH SCIENCES CENTER
- **Principal Investigator:** Nicholas Warren Gilpin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $328,500
- **Award type:** 5
- **Project period:** 2018-05-10 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9904464

## Citation

> US National Institutes of Health, RePORTER application 9904464, Alcohol and Traumatic Brain Injury; Neuronal and Behavioral Consequences (5R01AA025792-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9904464. Licensed CC0.

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