Central orexin-A increases colonic motility in conscious rats

► The effects of intracisternal orexin-A was tested in freely moving conscious rats. ► Central but not peripheral administered orexin-A enhanced fecal pellet output. ► Central orexin-A stimulated colonic contractions assessed by colonic manometry. ► Central orexin-A enhanced colonic motility. Increasing evidence has indicated that brain orexin plays a vital role in the regulation of gastrointestinal physiology such as gastric secretion, gastric motility and pancreatic secretion. However, little is known whether orexin in the brain is involved in the physiology of the lower gastrointestinal tract. The aim of this study was therefore to elucidate whether orexin-A in the brain is involved in the regulation of colonic motility. In this study, we measured fecal pellet output and recorded intraluminal colonic pressure waves in freely moving conscious rats to evaluate the effects of central orexin-A on colonic motor functions. Intracisternal but not intraperitoneal injection of orexin-A dose-dependently (1–10 μg) increased fecal pellet output. Findings obtained from manometric recordings revealed that intracisternal administration of orexin-A at a dose of 10 μg significantly enhanced colonic motor contractions. These results suggest for the first time that orexin-A acts centrally in the brain to enhance fecal pellet output and stimulate colonic motility in conscious rats. The present study would furthermore support our hypothesis that orexin-A in the brain may be an important candidate as a mediator of the cephalic phase gut stimulation including stimulated colonic motility in addition to well known physiological response such as stimulation of gastric acid and pancreatic acid secretion, and gastric motility.