Medullary serotonergic neurones modulate the ventilatory response to hypercapnia, but not hypoxia in conscious rats

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Abstract
Serotonergic neurones in the mammalian medullary raphe region (MRR) have been implicated in central chemoreception and the modulation of the ventilatory response to hypercapnia, and may also be involved in the ventilatory response to hypoxia. In this study, we ask whether ventilatory responses across arousal states are affected when the 5-hydroxytryptamine 1A receptor (5-HT1A) agonist (R)-(+)-8-hydroxy-2(di-n-propylamino)tetralin (DPAT) is microdialysed into the MRR of the unanaesthetized adult rat. Microdialysis of 1, 10 and 30 mm DPAT into the MRR significantly decreased absolute ventilation values during 7% CO2 breathing by 21%, 19% and 30%, respectively, in wakefulness compared to artificial cerebrospinal fluid (aCSF) microdialysis, due to decreases in tidal volume (VT) and not in frequency (f), similar to what occurred during non-rapid eye movement (NREM) sleep. The concentration-dependence of the hypercapnic ventilatory effect might be due to differences in tissue distribution of DPAT. DPAT (30 mm) changed room air breathing pattern by increasing f and decreasing VT. As evidenced by a sham control group, repeated experimentation and microdialysis of aCSF alone had no effect on the ventilatory response to 7% CO2 during wakefulness or sleep. Unlike during hypercapnia, microdialysis of 30 mm DPAT into the MRR did not change the ventilatory response to 10% O2. Additionally, 10 and 30 mm DPAT MRR microdialysis decreased body temperature, and 30 mm DPAT increased the percentage of experimental time in wakefulness. We conclude that serotonergic activity in the MRR plays a role in the ventilatory response to hypercapnia, but not to hypoxia, and that MRR 5-HT1A receptors are also involved in thermoregulation and arousal.