Morphine-induced stimulation of fetal breathing: role of mu 1-receptors and central muscarinic pathways.
The mechanism of action of low doses of morphine on breathing dynamics in the fetus was studied in 16 fetal lambs with chronically implanted electromyographic electrodes in the diaphragm. Morphine (0.15-2.5 mg/h) caused a significant dose-dependent increase in the number of diaphragmatic bursts per hour, with either an increase or no change in instantaneous breathing rate. There was also a significant dose-related increase in the continuity of the breathing pattern, as indicated by a decrease in the number of apneas per hour, and an increase in epoch duration. Morphine also had a significant effect on the stability of the breathing pattern, with an increase in the percentage of bursts that occurred in stable clusters. All of these effects were completely abolished by concurrent intracerebroventricular administration of either methylnaloxone or methylatropine or by pretreatment with intravenous naloxonazine. These results suggest that stimulation and stabilization of ventilatory activity in the fetal lamb by low doses of morphine are mediated via mu 1-receptors and involve central muscarinic pathways.
Szeto
H H
HH
Department of Pharmacology, Cornell University Medical College, New York, New York 10021.
Cheng
P Y
PY
Dwyer
G
G
Decena
J A
JA
Wu
D L
DL
Cheng
Y
Y
D000818:Animals; D001921:Brain / Q000502:physiology*; D003964:Diaphragm / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004576:Electromyography; D005333:Fetus / Q000502:physiology*; D009020:Morphine / Q000494:pharmacology*; D009116:Muscarine / Q000378:metabolism*; D011957:Receptors, Opioid / Q000502:physiology*; D017450:Receptors, Opioid, mu; D012119:Respiration / Q000187:drug effects*
D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D009020:Morphine; D009116:Muscarine