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Effects on Breathing and the CO2 Chemoreflex of 5‐HT and NK‐1 Receptor Antagonists in the Retrotrapezoid Nucleus (RTN)
Author(s) -
Dillard Matt L.,
Mouradian Gary,
Hodges Matthew R.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.894.13
Subject(s) - tidal volume , receptor , serotonin , chemistry , 5 ht receptor , wakefulness , ventilation (architecture) , anesthesia , neuroscience , pharmacology , medicine , respiratory system , biology , physics , electroencephalography , thermodynamics
Serotonin (5‐HT) and Substance P, typically increase the excitability of neurons within the neural network controlling breathing through G protein‐coupled receptors. These neuromodulators also stimulate pH/CO2 sensitive Phox2b‐expressing (Phox2b+) neurons in the retrotrapezoid nucleus (RTN), but their role in supporting the ventilatory CO2 chemoreflex within the RTN has not been tested in vivo. We hypothesize that unilateral antagonism in the RTN of 5‐HT and/or NK‐1 receptors will attenuate the ventilatory CO2 chemoreflex. To test this hypothesis, 8 week old male Sprague Dawley rats were chronically implanted with guide cannula unilaterally using stereotaxic coordinates previously published (Dias et al., 2008). After 7 or more days of recovery, microdialysis probes were inserted into the guide cannula for dialysis of mCSF alone followed by mCSF mixed with individual or a cocktail of antagonists to 5‐HT7 receptors (SB 269970 (100 μM)), 5‐HT2A receptors (MDL 11,939 (20 μM)) and/or NK‐1 receptors (SR 140333 (40 μM)) while measuring breathing in room air (35 min) and during a 7% CO2 challenge (10 min) before and during drug dialysis. We found that SB 269970 consistently reduced hypercapnic breathing frequency (−9 ± 2%, n=3) compared to mCSF alone, and had mixed effects on eupneic breathing and hypercapnic tidal volume. MDL‐11939 consistently reduced eupneic breathing frequency (−7 ± 0.4%, n=3) and hypercapnic tidal volume (−17 ± 0.8%, n=3) compared to mCSF alone, but had mixed effects on eupneic tidal volume and hypercapnic breathing frequency. In addition, a cocktail of all antagonists consistently increased eupneic breathing frequency (+14%, n=2) and decreased hypercapnic breathing frequency (−7 ± 0.4%, n=2) compared to mCSF alone. These preliminary data suggest 5‐HT and Substance P within the RTN may modulate breathing at rest and during hypercapnic conditions in vivo. Support or Funding Information This work was supported by NIH HL122358. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .