title: Augmented breaths ('sighs') are suppressed by morphine in a dose-dependent fashion via naloxone-sensitive pathways in adult rats.
abstract: Morphine treatment can eliminate augmented breaths (ABs; 'sighs') during spontaneous breathing. In the present study, unanesthetized rats were studied to: (1) determine the involvement of naloxone-sensitive receptor pathways, and (2) establish the dose-response relationship of this side effect. At a dosage of 5mg/kg (2-10mg/kg is recommended range for analgesia) morphine eliminated ABs from the breathing rhythm across nearly 100 min post-administration (vs. 6.2 ± 1.6 ABs in 15 min, control condition, p<0.001). This occurred despite no apparent effect on indices of ventilation. By contrast, when naloxone was co-administered with morphine, the occurrence of ABs was not different compared to control. The suppression of ABs by morphine followed a sigmoidal pattern across the low-mid dosage range (R(2)=0.83), whereas tidal volume and breathing frequency were unaffected. We conclude that the opioid-induced suppression of ABs is mediated by naloxone-sensitive opioid receptor pathways, and that this side effect is potent across the low-mid dosage range, and cannot be simply avoided by restricting dosage.
authors.affiliation: Division of Pulmonary and Critical Care, Department of Medicine, Penn State University College of Medicine, Hershey, PA 17033-0850, USA. hbell@hmc.psu.edu
authors.forename: Harold J
authors.initials: HJ
authors.lastname: Bell
authors.forename: Glenn
authors.initials: G
authors.lastname: Pankuch
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D010991:Plethysmography; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects*; D012137:Respiratory System / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009270:Naloxone; D009020:Morphine