Role of hypothalamic neuropeptide Y and orexigenic peptides in anorexia associated with experimental colitis in the rat

Neuropeptide Y (NPY) is thought to play a crucial role in the normal hypoth alamic response to starvation. After a period of food restriction, increase d release of NPY induces hunger and hyperphagia. and helps to restore body weight to its set point. Persistent anorexia in rats with experimental coli tis implies failure of this adaptive feeding response. In vivo NPY release and regional hypothalamic NPY concentrations were measured in rats with tri nitrobenzenesulphonic acid (TNBS)-induced colitis, healthy controls and ani mals pair-fed to match the food intake of the colitic group. Food intake in the colitic group was assessed after administration of NPY and two other p otent orexigenic peptides: melanin-concentrating hormone (MCH) and hypocret in (orexin-A). Food intake was decreased by 30-80% below control values for 5 days in the colitic rats. In both the pair-fed and colitic groups, relea se of NPY in the paraventricular nucleus was significantly increased compar ed with free-feeding controls. Intraventricular or intrahypothalamic admini stration of NPY, MCH or hypocretin elicited a feeding response in healthy c ontrols, but not in the colitic group. In summary, animals with TNBS-coliti s and anorexia show an appropriate increase in hypothalamic NPYergic activi ty. However. the failure of NPY and other orexigenic peptides to increase f eeding in the colitic group indicates suppression of feeding, either by inh ibition of a common downstream hypothalamic neuronal pathway or by inductio n of one or more potent anorexigenic agents.