Effect of intracerebroventricular orexin-B on food intake in sheep

Orexin is a hypothalamic neuropeptide that regulates feeding behavior in ra ts. Orexin-B has recently been cloned in pigs and was shown to stimulate fo od intake after intramuscular injection. This study was designed to determi ne whether intracerebroventricular (ICV) and intravenous injections of orex in could regulate appetite in sheep. Suffolk wethers were moved to indoor f acilities, adapted to diets for 6 wk, and trained to stand in stanchions fo r 3 to 6 h each day for 2 wk before indwelling ICV cannulas were installed. These sheep were provided water and they consumed feed ad libitum. On the day before an experiment, each sheep was cannulated in a jugular vein. On t he day of an experiment, sheep were placed in stanchions and allowed to sta nd for 1 h before use. Sheep were then monitored over a 2-h control period before i.v. injection with saline or porcine orexin-B (3 mug/kg BW) or ICV injection with artificial cerebrospinal fluid (CSF), orexin (0.03, 0.3, or 3 mug/kg BW) or in a second experiment with either orexin B (0.03, 0.3, 3 m ug/kg BW), neuropeptide-Y (NPY; 0.3 mug/kg BW), or orexin plus NPY. Food in take was monitored for consecutive 2-h periods. The i.v. injections of orex in did not affect food intake or metabolite or hormone concentrations. In I CV sheep, orexin increased food intake at 2 (P < 0.04) and at 4 h (P < 0.02 ). Food intake was greatest with the 0.3 mug/kg BW dosage of orexin (P < 0. 05). In the first 2 h after injection, orexin had an effect similar to that of NPY (0.23 kg for orexin and 0.2 kg for NPY). The combination of NPY and orexin had a greater effect on food intake (to 0.34 kg) than did either or exin (P < 0.05) or NPY (P < 0.008) alone. Differences were not apparent in the subsequent 2-h interval. No differences were noted in free fatty acid, glucose, growth hormone, luteinizing hormone, or insulin concentrations fol lowing orexin injection. There was an effect of ICV orexin treatment on pla sma cortisol concentrations (P < 0.002). Cortisol was increased by orexin a t the 0- to 2-h (P < 0.008) and in the 2- to 4-h (P < 0.009) intervals afte r orexin injection. These data indicate that central administration of orex in stimulates feed intake in sheep.