Serotonin (5‐HT) facilitates ventilation via distinct 5HT2 and 5HT4 receptor‐mediated mechanisms in situ, in the arterially perfused rat brainstem preparation

Abstract

Studies in vitro suggest that serotonin (5HT) neurons may be important for CO2 chemosensitivity. Their roles in modulating breathing in vivo, however, are unclear. We use a perfused in situ rat brainstem preparation that exhibits patterns of phrenic nerve discharge akin to breathing. Neuroventilation (NV) in this preparation is sensitive to the levels of CO2 equilibrating perfusion solutions (ranging between 3.5 and 9% CO2). We have shown that changes in NV associated with mild hypercapnia are abolished by inhibiting 5‐HT neurons. The present study was designed to identify post‐synaptic receptor subtypes involved in the control of breathing, and test the hypothesis that specific serotonergic mechanisms are critical for normal ventilatory control. Treatment with a 5HT2 antagonist (ketanserin; 5 and 10 uM) depresses NV under low CO2 conditions, indicating a 5HT2 mediated facilitation of NV under hypocapnea. Elevating CO2 (3.5 to 7%) reverses ketanserin‐induced NV depression, indicating CO2‐sensitive NV excitation, mediated through a mechanism other than 5HT2 receptor activation. Preliminary results suggest the balance may be due to 5HT4 activation in response to CO2, supporting a role for diverse serotonergic mechanisms in CO2 chemosensitivity in this preparation.Research supported by the NIH, NIMH and NINDS, Office of Minority Health Research SNRP program; grant number 5 U54 NS41069‐06A1