Study uncovers another way that opioid use, withdrawal affect the brain
Neurons in the brain are insulated by myelin, also called white matter, that acts like the rubberized coatings that cover electrical wires. Research from the Department of Psychology and the Biodesign Institute has shown that genes regulating myelin were suppressed during withdrawal from long-term opioid use. Photo by Antonio Avanti/Pexels
It's already understood that long-term opioid use and withdrawal both lead to changes the brain, some of which scientists are still mapping out.
Now, research from the Arizona State University Department of Psychology and Biodesign Institute has shown that these changes extend beyond just neurons, affecting the brain’s network of support cells.
Opioid withdrawal affected two genes that regulate oligodendrocytes, specialized support cells that help neurons communicate quickly and efficiently, according to the study, which was conducted using a mouse model and published in Pharmacology Biochemistry and Behavior.
Oligodendrocytes manufacture myelin, a bright-white fatty substance that wraps around nerve fibers and insulates them. Myelin is nicknamed “white matter” in the brain, even though its insulating actions are analogous to the colored rubberized coatings that cover the wires in light fixtures and smoke detectors in our homes. When myelin is damaged, it can cause problems ranging from parts of the body feeling tingly to cognitive deficits.
“Repeated exposure to opioids followed by withdrawal resulted in changes to two genes involved in the process of myelination in the prefrontal cortex, a part of the brain that is responsible for higher-order thinking. These findings suggest that opioid use and withdrawal might affect white matter in this region, potentially impacting functions such as decision-making and self-control,” said Olivia Law, psychology graduate student and first author on the paper.
Reduced myelin-related gene expression and social interactions
Because social environment plays an important role in drug use and relapse, the researchers assessed changes in social behavior and gene expression in the brain during early stages of opioid withdrawal.
During the first 48 hours of withdrawal, fewer social interactions were reported and the expression levels of two genes that regulate oligodendrocyte function were also reduced. One gene, Tcf712, is important in guiding oligodendrocytes to start the process of making myelin. The other, Klk6, is involved in later stages of myelination, including repairing damage.
“These and other findings suggest that changes in myelin contribute to addiction by altering the sensitivity of reward brain pathways to drugs of abuse. ... Understanding the underlying gene expression changes is critically important,” said Jessica Verpeut, assistant professor of psychology, associate faculty with the Neurodegenerative Disease Research Center and senior author on the study.
The importance of support cells to neuropsychiatric disorders
Because of the sensitivity of myelin to opioid use, controlling the growth and restructuring of myelin by restoring oligodendrocyte function could be a therapeutic target for opioid addiction and withdrawal, the study findings suggest.
“This work highlights that to better understand and treat opioid addiction — and other neuropsychiatric disorders — requires studying not just neurons but also several other cell types that support neuronal function,” said Jonathan Gewirtz, professor of psychology.
About the study
This study was funded by the Institute for Mental Health Research, Institute for Social Science Research, Nancy Eisenberg Junior Faculty Scholar Award, Arizona Department of Health Sciences (grant number ADHS14-052688), National Institute on Drug Abuse (grant number U01 DA051993), U.S. Department of Health and Human Services and the State of Arizona (grant number CTR057001), National Institute on Aging (grant number P30AG019610), Arizona Alzheimer’s Disease Research Center REC Fellows Program and Arizona Alzheimer’s Consortium.
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