Biphasic effects of morphine on bulbar respiratory neuronal activities in decerebrate cats.
To understand neuronal mechanisms underlying respiratory depression induced by morphine, membrane potential, input resistance and burst discharge in different types of respiratory neurons were recorded in decerebrate and vagotomized cats. Intravenous morphine (0.3-3.0 mg/kg) dose-dependently decreased the respiratory discharge in the phrenic and iliohypogastric nerves. The drug changed the respiratory frequency in a biphasic fashion, a transient increase (early phase) followed by a long-lasting decrease (late phase). During the early phase, the membrane was hyperpolarized throughout the respiratory cycle and the burst discharge was decreased in all types of respiratory neurons. During the late phase, the active phase depolarization and the inactive phase hyperpolarization were decreased, resulting in a decline of membrane potential fluctuations. Input resistance was decreased during the early phase and increased during the late phase. Iontophoresed (50-100 nA) morphine produced hyperpolarization of the membrane and a decrease in input resistance in respiratory neurons. This hyperpolarization remained unaltered after iontophoresed tetrodotoxin depressed the synaptic transmission. These effects of morphine were completely blocked by naloxone and beta-funaltrexamine, but not by naltrindole. The present results suggest that morphine depresses the respiratory neuronal activity through two different mechanisms, both of which are mediated by mu receptors.
Haji
Akira
A
Department of Pharmacology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, 930-0194, Toyama, Japan.
Okazaki
Mari
M
Ohi
Yoshiaki
Y
Yamazaki
Hiromi
H
Takeda
Ryuji
R
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002415:Cats; D003655:Decerebrate State; D005260:Female; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009020:Morphine / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology; D012119:Respiration / Q000187:drug effects*; D012131:Respiratory Insufficiency / Q000139:chemically induced / Q000503:physiopathology
D009020:Morphine