Orexinergic modulation in amphibians and mammal

Physiology 2015 (Cardiff, UK) (2015) Proc Physiol Soc 34, SA054

Research Symposium: Orexinergic modulation in amphibians and mammal

L. H. Gargaglioni1

1. Animal Morphology and Physiology, Sao Paulo State University, Jaboticabal, Sao Paulo, Brazil.

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Orexins (or hypocretins) play an important role in the modulation of respiratory control in mammals, but there are no data describing the role of the orexinergic system in the peripheral and central chemoreception of non-mammalian vertebrates. Thus, the aim of this study was to examine the localization of orexin-immunoreactive neurons in the brain of toads (Rhinella schneideri) and to investigate the contribution of orexin receptor-1 (OX1R) to the hypoxic (5%O2) and hypercarbic (5%CO2) ventilatory responses during light and dark phases by intracerebroventricular (i.c.v.) injections of SB-334867 (OX1R selective antagonist; dose: 5 and 10mM). In addition, we injected SB-334867 (OX1R antagonist, 5 mM) into the locus coeruleus (LC) of male Wistar rats and measured ventilation (VE) using a whole-body plethysmograph, together with EEG and EMG during normocapnia and hypercapnia. In toads, our results demonstrated that the SB-334867 attenuated the ventilatory response to hypercarbia during the dark phase in 54.8% by acting on tidal volume (vehicle: 172.9±5.3% of baseline; SB-334867: 114.2±9.8% of baseline) and breathing frequency (vehicle: 218.3±24.1% of baseline; SB-334867: 134.8±7.8% of baseline), while during the light phase, attenuated the ventilatory response to hypoxia in 51.6% by acting on tidal volume only (vehicle: 230.9±33.4% of baseline; SB-334857: 127.5±4.9% of baseline). As to mammals, SB-334867 injection caused a significant attenuation of the hypercapnic ventilatory response during wakefulness (ΔVE vehicle= 1010 mL.Kg-1.min-1 vs ΔVE vehicle= SB-334867 = 793 mL.Kg-1.min-1) but not during sleep (ΔVE vehicle= 747 mL.Kg-1.min-1 vs ΔVE vehicle= SB-334867 = 703 mL.Kg-1.min-1). We conclude that in R. schneideri, orexinergic neurons are located in the suprachiasmatic nucleus and OX1R contributes to hypercarbic and hypoxic chemoreflexes. In rats, OX action on OX1R in the LC exerts an excitatory modulation in the hypercapnic chemoreflex during walkefullness. Financial support: FAPESP, INCT-FisComp, UNESP and CNPq



Where applicable, experiments conform with Society ethical requirements.

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