Abstract
We examined whether the chemoreceptor reflex in prepro-orexin knockout mice was blunted or not, and if so, whether supplementation of exogenous orexin restore the abnormality. In addition, we studied whether pharmacological blockade of orexin in the wild-type mice resulted in a similar abnormality. A cannula for intracerebroventricular injection to the lateral ventricle was implanted to the isoflurane-anesthetized mice together with electrodes for recording electroencephalogram and electromyogram. Ventilation was recorded by whole body plethysmography after recovery period of at least 7 days. After recording of baseline breathing for 1 hr, orexin-A, -B, an orexin receptor antagonist, or vehicle was intracerebroventriculary injected and hypercapnic or hypoxic gas mixture was introduced into the recording chamber for 10 min. Data were examined for only awake period because sleeping distorts chemoreflex sensitivity. Hypercapnic ventilatory responses but not hypoxic responses were attenuated in orexin knockout mice as compared to those in the wild-type littermates. Similar abnormality was reproduced in wild-type mice treated with orexin antagonist. Intracerebroventricular injection of orexin partially restored the hypercapnic chemoreflex in the mutant mice. Our findings suggest that orexin plays a crucial role for CO2-sensitivity at least during awake periods. [J Physiol Sci. 2006;56 Suppl:S76]
