Neurotransmissão orexinérgica no Locus coeruleus : participação na resposta ventilatória à hipercapnia na vigília e sono nas fases clara e escura em ratos não anestesiados

Abstract

The orexins are hypothalamic neuropeptides involved in an array of functions such as regulation of sleep/wake states and chemoreception to CO2/pH. The Locus coeruleus (LC) is a chemosensitive site and expresses an extensive population of orexin receptor 1 (OX1R). Here we tested the hypothesis that OX1Rs located in the LC participate in the ventilatory response to hypercapnia in a vigilance state and diurnal cycle-dependent manner. To this end, we performed unilateral injections of SB-334867 (OX1R antagonist, 5 mM) into the LC of male Wistar rats and evaluated the ventilatory response to 7% CO2 during wakefulness and sleep in the dark and light phase of the diurnal cycle. Hypercapnia induced an increase in ventilation in all groups compared to normocapnic values. However, the injection of (SB-334867) promoted an attenuation of the hypercapnic chemorreflex during wakefulness, due to changes in VT. In addition, microinjection of SB-334867 decreases the wakefulness time during dark phase. We suggest that projections of orexin-containing neurons to the LC contribute, via OX1Rs, to the hypercapnic chemoreflex during wakefulness in the dark phase.