Fentanyl causes symptoms that can lead to death from overdose. One of these symptoms is slow breathing, which deprives drug users of oxygen. New in JNeurosci , Erica Levitt and colleagues, from the University of Michigan Medical School, explored mechanisms for combating slow breathing from fentanyl. More specifically, the researchers used mice to examine mechanisms in the hypothalamus, a brain region that influences how breathing changes based on internal states.
The research team found that high carbon dioxide levels affected the activity of neurons in the hypothalamus that make orexin, which is a peptide that controls sleep and arousal. Altering the activity of these neurons increased breathing rates in mice. This manipulation also reversed slow breathing from fentanyl. Levitt and colleagues targeted another signaling system (glutamate) to trigger breathing and found that this mechanism worked independently of orexin. Manipulating glutamate neurons directly in the hypothalamus alleviated slow breathing from fentanyl. Finally, the researchers found that artificially activating hypothalamus neurons that express both mechanisms increased breath rate, but in a manner that required orexin signaling.
According to Levitt, this work suggests that an orexin and glutamate-expressing neuron population in the hypothalamus may be a potential treatment target for the harmful effects of fentanyl on breathing.
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About JNeurosci
JNeurosci was launched in 1981 as a means to communicate the findings of the highest quality neuroscience research to the growing field. Today, the journal remains committed to publishing cutting-edge neuroscience that will have an immediate and lasting scientific impact, while responding to authors' changing publishing needs, representing breadth of the field and diversity in authorship.
About The Society for Neuroscience
The Society for Neuroscience is the world's largest organization of scientists and physicians devoted to understanding the brain and nervous system. The nonprofit organization, founded in 1969, now has nearly 35,000 members in more than 95 countries.
JNeurosci
10.1523/JNEUROSCI.0550-26.2026
Hypothalamic Glutamatergic/Orexinergic Neurons Attenuate Fentanyl-Induced Respiratory Depression via Medullary Prebötzinger Complex Pathways
20-Jul-2026
The authors declare no competing financial interests.