# Determination of factors that influence addiction-related outcomes following brain injury

> **NIH VA I01** · CLEMENT J. ZABLOCKI VA MEDICAL CENTER · 2020 · —

## Abstract

Each year, an estimated 1.7 million Americans suffer from traumatic brain injury (TBI). The incidence of TBI
among veterans of the military may be as high as 30%, with blast injury from explosive devices causing the
overwhelming majority of TBIs in combat settings. An association between non-severe (i.e., mild or moderate)
mTBI and substance abuse has been demonstrated in numerous epidemiological studies. Therefore, veterans
of the military that have experienced TBI during deployment or during non-deployed and civilian life may be at
higher risk for drug abuse disorders than people that have not experienced TBI. However, despite extensive
evidence of increased substance abuse disorder following non-severe TBI, little is known about how traumatic
brain injury changes brain structure and function to make somebody more susceptible to drug abuse. Thus, there
is a great deal of inconsistency in clinical treatments prescribed to non-severe TBI sufferers that can include no
drug treatment, non-steroidal anti-inflammatory drugs, or even opioids. The long-term consequences for millions
of veterans remains unknown.
Advanced magnetic resonance imaging (MRI) techniques (e.g., diffusion tensor imaging) in humans have
revealed subtle damage to brain tissues following mTBI, in which specific brain regions seem to be particularly
vulnerable to injury. In our published data, an experimental model of blast mTBI in rodents led to an enduring
inflammatory response that was evident in the medial prefrontal cortex (mPFC) of the brain, which was evident
using advanced MRI techniques and pathological investigation. There is emerging evidence of a link between
these types of inflammatory responses in the brain and drug abuse behavior. In fact, recent research has
indicated that the use of opioids, which are commonly prescribed for TBI, initiate similar inflammatory responses.
Therefore, our hypothesis is that drug intake and/or drug abuse relapse would be more likely following mTBI.
Given that opioids are commonly administered to mTBI patients in emergency departments, combined with the
fact that over 13 million Americans misused prescription pain killers or used heroin in 2016, this could lead to a
significant public health issue with mTBI patients that are treated with opioids suffering from possible life-long
issues with drug dependency.
This study will explore the relationship between mTBI and substance abuse disorder using a laboratory model,
wherein rodents will be exposed to blast mTBI and post-injury opioid self-administration to model individual drug
treatment following injury. After removal of opioids, rodents will later be exposed again to opioid self-
administration to identify relapse behaviors and addiction liability. The effects of pharmacological treatment on
addiction liability will also be defined. The mechanisms for these changes in the brain following mTBI and opioid
exposure will be determined using advanced MRI techniques and analysis of brain struc...

## Key facts

- **NIH application ID:** 9948172
- **Project number:** 1I01RX002931-01A2
- **Recipient organization:** CLEMENT J. ZABLOCKI VA MEDICAL CENTER
- **Principal Investigator:** BRIAN D STEMPER
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2020-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948172

## Citation

> US National Institutes of Health, RePORTER application 9948172, Determination of factors that influence addiction-related outcomes following brain injury (1I01RX002931-01A2). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9948172. Licensed CC0.

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