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Antagonism of Orexin Receptor 1 (OX1) in the Locus coeruleus (LC) decreases the Hypercapnic Ventilatory Response in Unanesthetized Rats during Wakefulness
Author(s) -
Vicente Mariane,
Dias Mirela,
Bicego Kenia,
Gargaglioni Luciane
Publication year - 2015
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.29.1_supplement.860.7
Subject(s) - locus coeruleus , wakefulness , orexin , antagonism , medicine , narcolepsy , anesthesia , neuroscience , receptor , central nervous system , biology , pharmacology , electroencephalography , neuropeptide , modafinil
Orexin (OX) plays an important role in the control of ventilation and OX neurons send extensive projections to LC. We hypothesized that OX acting on OX1R in the LC exerts an excitatory modulation in CO 2 ‐drive to breath in a vigilance state‐dependent manner. To this end, we injected SB‐334867 (OX1R antagonist, 5 mM) into the LC of male Wistar rats and measured ventilation (V E ) using a whole‐body plethysmograph, together with EEG and EMG during normocapnia and hypercapnia. SB‐334867 injection caused a significant attenuation of the hypercapnic ventilatory response during wakefulness (ΔV E vehicle= 1010 mL.Kg ‐1 .min ‐1 vs ΔV E SB‐334867 = 793 mL.Kg ‐1 .min ‐1 ) but not during sleep (ΔV E vehicle= 747 mL.Kg ‐1 .min ‐1 vs ΔV E SB‐334867 = 703 mL.Kg ‐1 .min ‐1 ). The effect of SB‐334867 was in tidal volume. Basal ventilation was not affected by OX1R antagonism in the LC. These results suggest OX action on OX1R in the LC exerts an excitatory modulation in the hypercapnic chemoreflex during wakefulness. Financial Support: FAPESP and CNPq.