Fentanyl effects on breath generation in C57BL/6J and A/J mouse strains

• This work addresses whether genetic background is a factor in opioid-induced respiratory depression.
• Utilized a strain-by-fentanyl approach to test responses in pause-prone vs pause-resistant mouse strains.
• Pauses not enhanced in pause-prone and not produced in pause-resistant.

We examined the effect of fentanyl on chemoresponsiveness in mouse strains divergent in the expression of spontaneous and post-hypoxic pauses. Frequency and tidal volume were recorded with plethysmography in A/J and C57BL/6J (B6) male mice. Mice selected at random received an intraperitoneal (IP) injection of either saline, low dose fentanyl (LDF = 0.04 mg/kg), or high dose fentanyl (HDF = 0.4 mg/kg) under hypoxia (8% O2) or hyperoxia (100%O2). LDF produced a decrease in frequency during hypoxia in B6, but not A/J, mice. HDF significantly decreased frequency and tidal volume in both strains under hypoxia and hyperoxia (p < 0.01); naloxone, an opioid antagonist, reversed this response. The acute administration of fentanyl at any dose did not promote apneas in strains of mice exhibiting regular or irregular respiratory patterns. However, higher doses depressed respiratory frequency in both strains. The B6 mice responded with a depressive response to hypoxia that did not recover with reoxygenation, but did recover with time or naloxone.