Effects of serotonin receptor blockade by methysergide on loaded breathing in the rabbit

Previous works demonstrated that the excitatory role of serotonin (5-hydroxytryptamine, 5-HT) on ventilation is mediated by 5-HT1,2 receptors stimulation. We hypothesized that load-induced hypoventilation could be minimized by a central release of 5-HT. Conversely, blockade of 5-HT receptors should accentuate hypoventilation. We compared the ventilatory effects of methysergide (MS), a 5-HT1,2 receptors antagonist, in 3 groups of anesthetized, spontaneously breathing rabbits: (1) a group of animals breathing for 60 min through a 370 cm H2O.liter-1.s inspiratory resistive load (IRL group), whose paCO2 increased with IRL; (2) a Control group; (3) a Control + CO2 group, made hypercapnic to assess the possible effect of this stimulus on the ventilatory responses to MS. In the 3 groups, i.v. injection of MS induced the same ventilatory changes, characterized by a rapid shallow breathing with a shorter integrated diaphragmatic activity. This confirms the tonic facilitatory effect of 5-HT on ventilation and suggests that IRL would not increase 5-HT release in the sites close to the respiratory nuclei.