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.
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