Locus Coeruleus activity correlates with transient elevations in breathing during opioid-induced respiratory depression

Fentanyl increases locus coeruleus burst frequency and couples it to transient breathing elevations in mice, and LC-coupled ventilation persists after five days of repeat opioid use.

• Why it matters: A history of opioid use is a major overdose risk, but how it reshapes locus coeruleus activity and the magnitude of opioid-induced respiratory depression is not well understood.
• What they did: Using plethysmography and fiber photometry, mice were tested with fentanyl before and after five days of repeat opioid use, measuring locus coeruleus bursts and opioid-induced respiratory depression.
• The result: After repeat opioid use, opioid-induced respiratory depression diverged: adaptive ventilatory response mice showed smaller OIRD with reduced LC-Ve gain, while non-adaptive response mice showed unchanged reliance on LC-Ve.

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