Central orexin-A changes the gastrointestinal motor pattern from interdigestive to postprandial in rats

Orexin-A, also described as hypocretin-I, was discovered in the extracts of the rat brain. OXA is implicated in a wide variety of physiological functions, such as feeding, arousal, behavioral activity, energy homeostasis and gastrointestinal motility. Orexin receptor type-1 is highly expressed in the dorsal motor nucleus of vagus. Although peripherally administered OXA abolishes small intestinal interdigestive contractions in rats, it still remains unclear whether central OXA affects interdigestive GI motility in rats. Two strain gauge transducers were attached on the antrum and duodenum to record circular muscle contractions. Spontaneous gastroduodenal contractions were recorded in freely moving conscious rats. OXA (1-20 µg) was administered intracerebroventricularly (i.c.v.). Atropine pretreatment (1 mg/kg, i.p.) and truncal vagotomy were performed to elucidate the neural pathways of central OXA. OXA (1-20 µg) dose-dependently disrupted the interdigestive phase III-like contractions and induced an irregular postprandial-like motility pattern in the stomach and duodenum. The stimulatory effect of OXA on gastroduodenal postprandial-like motility pattern was abolished by atropine and truncal vagotomy. Central administration (i.c.v.) of selective OXA receptor antagonist, SB-334867 (16 µg), enhanced gastric spontaneous phase III-like contractions. It is suggested that central OXA changes GI motor pattern from interdigestive to postprandial via the vagal cholinergic pathways. Endogenous OXA may have an inhibitory role in interdigestive GI motility in rats.