Abstract
We examined whether the chemoreceptor reflex in prepro-orexin gene knockout mice was blunted or not, and if so, whether supplementation of exogenous orexin restored the 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 20 min, either orexin or vehicle was intracerebroventriculary injected and hypercapnic (5% or 10% CO2, 21% O2, residual N2) or hypoxic (15% or 10% O2) gas mixture was introduced into the recording chamber for 5 min. Data were examined for only awake period because sleeping is known to distort chemoreflex sensitivity. Hypercapnic ventilatory responses but not hypoxic responses were attenuated in orexin knockout mice as compared to those in the wild-type littermates. 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. [Jpn J Physiol 55 Suppl:S106 (2005)]
