Fentanyl effects on breath generation in C57BL/6J and A/J mouse strains.
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.
Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Linnea
L
Fechtner
Louis Stokes Department of Veteran Affairs Medical Center, Cleveland, OH, USA; Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Mazen
M
El Ali
Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Abdus
A
Sattar
Louis Stokes Department of Veteran Affairs Medical Center, Cleveland, OH, USA.
Michael
M
Moore
Louis Stokes Department of Veteran Affairs Medical Center, Cleveland, OH, USA; Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA. Electronic address: kpstrohl@aol.com.
Kingman P
KP
Strohl
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005283:Fentanyl / Q000494:pharmacology*; D000860:Hypoxia / Q000188:drug therapy; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D010991:Plethysmography; D012119:Respiration / Q000187:drug effects*; D013045:Species Specificity; D013990:Tidal Volume / Q000187:drug effects; D013997:Time Factors
D000701:Analgesics, Opioid; D005283:Fentanyl
Apnea; Genetic background; Hypoxia; Ventilatory control