TNF-induced anorexia and learned food aversions are attenuated by area postrema lesions

Tumor necrosis factor (TNF) or cachectin has been proposed as an important mediator of cancer anorexia and cachexia. The present studies examined the extent to which TNF administration generates symptoms similar to those produced by tumor growth. Like the growth of certain tumors, TNF administration was found to be associated with the development of strong aversions to a novel diet. Area postrema lesions were found to significantly attenuate the effects of TNF on intake of a novel diet, a finding previously reported for tumor anorexia. In addition, the anorexic effects of TNF differed considerably as a function of the novelty of the diet. When the available diet was novel, effects of TNF in lowering food intake were substantial, whereas more modest effects were seen when the diet was familiar. These findings provide evidence for parallels between TNF- and tumor-induced anorexias. Nonetheless, these studies also confirm previous observations of the rapid development of tolerance to the anorexic effects of TNF, a finding that is not consistent with a role for TNF as a critical mediator of tumor anorexia.