Rethinking the Brain’s Response to Opioids
NYMC Researchers Reveal Findings That Could Inform More Targeted Approaches to Addiction Treatment
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A study by New York Medical College faculty researchers, published in the Journal of Neuroscience, offers new insight into how the brain responds to repeated opioid exposure and challenges some long-standing assumptions along the way. Focusing on orexin, a brain peptide known to regulate wakefulness, motivation, and reward, the research reveals that opioids may disrupt this system in unexpected ways.
“Orexin has long been recognized as a key player in arousal and motivation, and more recently in opioid addiction,” says Elizabeth Berry, Ph.D. ’23, assistant professor of cell and molecular physiology and lead author of the study. “What surprised us was that repeated opioid exposure didn’t appear to strengthen this system, as many had assumed. Instead, we found signs that parts of the orexin system may actually become less responsive over time, which changes how we think about its role in driving drug-seeking behavior.”
Repeated opioid exposure produces structural changes in orexin neurons, making them more compact and increasing their orexin peptide content. This had been interpreted to mean that in the addicted state, orexin release would be enhanced; however, this was not the case. Using precise electrical measurements, the researchers found that repeated morphine exposure actually impaired the ability of orexin neurons to generate the electrical impulses necessary to release orexin peptide.
Another unexpected finding was that only one of the two known subtypes of orexin neurons was impaired in its ability to generate impulses, indicating that the two subtypes play previously unrecognized, distinct roles in the development of substance use disorder.
“The findings open the door to a better understanding of substance use disorders and could help guide the development of more targeted treatments in the future,” says Christopher Leonard, Ph.D., professor of cell and molecular physiology, director of neuroscience, and senior author on the study.
The researchers now plan to explore the mechanisms that cause these impairments to determine if they can be reversed and work to define the specific roles the two subtypes of orexin neurons play in regulating arousal and motivation.
