Key Insights
UAB researchers have received a $3.3 million NIDA grant to investigate a newly identified brain cell population linked to opioid addiction, relapse risk and genetic influences, advancing potential treatments for opioid use disorder.
Olivia Drake, a current a Medical Scientist Training Program student, is leading a study funded by the National Institute on Drug Abuse.Opioid use disorder is a public health crisis that affects millions of individuals across the United States. With the increasing use of potent opioids like fentanyl and heroin, available treatments for opioid use disorder are often unsuccessful.
A $3.3 million grant from the National Institute on Drug Abuse to the lab of Jeremy Day, Ph.D., professor and vice chair for Strategic Planning and Recruitment in the Department of Neurobiology at the University of Alabama at Birmingham, will help his team research the neuroscience behind opioid use disorder.
The project, titled “A Novel Cellular and Circuit Target for Opioids,” is a collaborative, interdisciplinary area of investigation led by Olivia Drake, a Medical Scientist Training Program student in the Graduate Biomedical Sciences Genetics, Genomics and Bioinformatics theme. Other collaborators in the Department of Neurobiology are Jamie Peters, Ph.D., associate professor, and Jasper Heinsbroek, Ph.D., associate professor.
Understanding opioid addiction in the brain
The nucleus accumbens is a defined subcortical brain structure that plays an essential role in pleasure, reward and motivation. Previous research has shown that this brain region is an important site that mediates the addictive properties of many drugs of abuse.
Until recent technological advances, researchers lacked a complete understanding of the cellular composition of this important brain structure.
“Using a sophisticated new approach to create a cellular atlas of the nucleus accumbens, we identified an unusual neuronal population that expresses high levels of the mu opioid receptor, which is essential for the behavioral effects of opioid drugs,” Day said.
Jasper Heinsbroek, Ph.D. and Jamie Peters, Ph.D. This receptor is produced by a gene called Oprm1, which serves as the main target of opioids like heroin and fentanyl, and is part of the brain pathway that controls the desire and pleasurable feelings they produce.
“In humans, initial positive feelings following opioid experience are a major risk factor for subsequent addiction, which drives overdose risk,” Day said. “This is important because opioid overdose deaths are a major health crisis in Alabama and the United States.”
Understanding how opioids affect cells in the nervous system will provide scientists with the fundamental knowledge to treat and prevent opioid addiction.
A new target for understanding opioid addiction
The rare neuronal population identified by the Day Lab exists across species, including humans. Little information is known about how these cells operate or how they contribute to the rewarding effects of opioids.
Using newly developed animal models and gene-editing tools, researchers will identify, track and control these cells while testing whether the cells are important for the rewarding effects of opioids and whether they contribute to relapse that occurs when an individual returns to opioid use after a drug-free period.
The Day Lab will investigate how genetics may influence an individual’s risk of developing opioid use disorder.
“Genetic differences in humans alter the expression and function of genes in brain structures like the nucleus accumbens. This work will help to identify human-relevant targets of opioids, while also providing insight into how genetic variation in humans may contribute to addiction risk,” Day said.