Breathing stimulation mediated by 5-HT1A and 5-HT3 receptors within the preBötzinger complex of the adult rabbit

Serotonin (5-HT) has been reported to play excitatory effects on respiration by acting on preBötzinger complex (preBötC) neurons in neonatal or juvenile rodents. However, whether its action is circumscribed to the preBötC and present in other animal species, particularly in adult preparations, is unknown. We investigated the respiratory role of 5-HT within the preBötC and neighbouring respiration-related regions. Experiments were performed on α-chloralose-urethane anesthetized, vagotomized, paralyzed and artificially ventilated rabbits making use of bilateral microinjections (30-50 nl). 5-HT caused excitatory effects on respiratory activity only when applied to the preBötC. These effects were mediated by 5-HT1A and 5-HT3 receptors as shown by microinjections of specific agonists of the different types of 5-HT receptors. Unexpectedly, the blockade of 5-HT1A receptors by methysergide or the specific antagonist (S)-WAY 100135 induced excitatory respiratory effects. Microinjections of the 5-HT3 receptor antagonist ondansetron did not influence respiration, but prevented (S)-WAY 100135-induced responses. The blockade of GABAA receptors by bicuculline within the preBötC prevented the effects of the 5-HT1A receptor agonist 8-OH-DPAT. The involvement of GABAergic inhibition and 5-HT1A receptor-mediated disinhibition is also corroborated by immunohistochemical data. The results show for the first time in an adult animal preparation that 5-HT plays a pivotal role in the modulation of the preBötC activity probably via both presynaptic and postsynaptic mechanisms and highlight the importance of disinhibition phenomena. Present findings may be relevant to some respiratory disorders in which an impairment of central 5-HT mechanisms has been reported, such as sleep apnoea and sudden infant death syndrome.