Evidence that respiratory depression by serotonin agonists may be exerted in the central nervous system

Resting with CO2 stimulated respiration were measured by means of a whole body plethysmograph in rats lightly anesthetized with halothane. The respiratory effects of different doses of the serotonin precursor 5-HTP, and the serotonin agonist 5-methoxy-N,N-dimethyltryptamine were studied as well as the effects of a serotonin antagonist methysergide and p-chlorophenylalanine, an inhibitor of serotonin synthesis. The serotonergic agonists decreased tidal volume and minute volume in a dose dependent manner and produced a respiratory acidosis. The respiratory depressant effect was antagonized by methysergide, and the serotonergic antagonist and synthesis inhibitor alone stimulated respiration. Rats given intraventricular 5-methoxy-N,N-dimethyltryptamine also evidenced a decrease in tidal volume, and this response was greater in animals given 5,7-dihydroxytryptamine. It seems likely that CNS serotonin receptors are involved in the control of both basal and CO2 stimulated respiration.