Role of monoaminergic systems in morphine-induced respiratory depression

The respiratory response to morphine sulfate was assessed in rats pretreated with different modifiers of noradrenergic and serotonergic activity and, additionally, the respiratory depression was related to the brain levels of the two amines, serotonin (5-HT) and norepinephrine (NE). At respiratory depressant doses, morphine induced an increase in 5-HT and a decrease in NE levels in the medullapons area. The time sequence of respiratory depression correlated with a decline in NE and a rise in 5-HT levels. Pretreatments which increased 5-HT levels potentiated the respiratory depression and agents which increased NE levels antagonized the depression. A system of antagonistic modulation by the two amines of morphine-induced respiratory depression is proposed, whereby 5-HT functions as a depressant mediator and NE as an excitatory mediator. Naloxone appears to reverse the respiratory depression by altering the serotonergic component of the action of morphine.