The role of serotonergic (5-HT) neuromodulation in respiratory chemosensitivity

Abstract

Breathing must be regulated to maintain appropriate levels of oxygen and carbon dioxide. Breathing may be influenced by serotonergic (5-HT) neurons, sensitive to CO₂, which activate the brain's respiratory network. However, this role of 5-HT neurons as CO₂-sensitive chemoreceptors in unanesthetized animals is unclear. This study used an unanesthetized in situ perfused rat brainstem preparation to test the hypothesis that 5-HT neurons contribute to CO₂ ventilatory responses. Changes in phrenic nerve discharge patterns were monitored as gas-saturated solutions supplying the preparation were switched from 5%C0₂ to 7%C0₂ (balance 0₂). The importance of 5-HT neurons was identified by comparing responses before and after application of the specific serotonin 1A receptor agonist 8-hydroxy-(dipropylamino) tetralin hydrobromide (8-OH-DPAT; at doses of 0, 1.5, 3, and 6 uM in the perfusate). The action of 8-OH-DPAT is to inhibit 5-HT neurons and reduce synaptic 5-HT release. Results indicated that changes in phrenic burst pattern similar to hypercapnic ventilatory responses observed in vivo, were greatly disrupted by 8-OH-DPAT treatment. These results illustrate that activation of 5-HT neurons is critical for CO₂ chemosensitivity in this in situ preparation and suggest that these neurons may play a key role in the regulation of breathing in otherwise intact animals.