Serotonergic mechanisms are necessary for central respiratory chemoresponsiveness in situ

Evidence from in vivo and in vitro experiments conclude that serotonin (5-HT) neurons are involved in and play an important role in central respiratory CO2/H+ chemosensitivity. This study was designed to assess the importance of 5-HT neurons and 5-HT receptor activation in the frequency and amplitude components of the hypercapnic response of the respiratory network in the unanesthetized perfused in situ juvenile rat brainstem preparation that exhibits patterns of phrenic nerve discharge similar to breathing in vivo. Exposure to a hypercapnic perfusate increased phrenic burst frequency and/or amplitude, the neural correlates of breathing frequency and tidal volume in vivo. Hypercapnic responses were also assessed during exposure to ketanserin (5-HT2 receptor antagonist), and 8-OH-DPAT (inhibiting 5-HT neurons via 5-HT1A autoreceptors). Neither of these drugs substantially altered baseline activity, however, both abolished hypercapnic responses of the respiratory network. These data illustrate that 5-HT neurons and 5-HT receptor activation are not required for respiratory rhythm generation per se, but are critical for CO2 responses in situ, supporting the hypothesis that 5-HT neurons play an important role in central ventilatory chemosensitivity in vivo.

► We assess the role of 5-HT neurons and receptors in the hypercapnic response of the in situ rat brainstem preparation.
► Exposure to hypercapnia increased phrenic burst frequency and/or amplitude.
► Hypercapnic responses were abolished when exposed to ketanserin (5-HT2 receptor antagonist).
► Hypercapnic responses were abolished when exposed to 8-OH-DPAT (5-HT1a agonist, inhibits firing of serotonergic neurons).