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

Abstract

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.

Effects of acute and repeated administration of Staphylococcal enterotoxin A on Morris water maze learning, corticosterone and hippocampal IL-1β and TNFα

“…For example, previously experienced foods are not rejected in SEA or SEB challenged mice, but new foods provided in a new environment result in significant reduction of intake (Kusnecov et al , 1999; Kawashima & Kusnecov, 2002; Rossi-George et al , 2005). Centrally, this was shown to be CRH-dependent (Kaneta & Kusnecov, 2005), and linked to TNFα production (Rossi-George et al, 2005), a finding consistent with evidence in rats that TNFα administration reduces food intake if the food is novel (Bernstein et al , 1991). Finally, due to the involvement of CRH and HPA axis activation, it was hypothesized that these behaviors might have involved increased levels of anxiety after SEA challenge.…”

Regulation of bitter taste responses by tumor necrosis factor

“…sickness behavior) which include fatigue, malaise, depression, and anorexia. It has been shown that administration of recombinant TNF induces significant reduction in food intake both in rodents and in humans (Bernstein et al, 1991; Michie et al, 1989; Spiegelman and Hotamisligil, 1993). How TNF regulates food intake remains incompletely understood.…”

“…How TNF regulates food intake remains incompletely understood. Both peripheral and brain mechanisms are likely involved (Bernstein et al, 1991; Dantzer, 2001; Plata-Salaman, 1998). …”

Mouse Tumor Necrosis Factor-α Increases Brain Tryptophan Concentrations and Norepinephrine Metabolism While Activating the HPA Axis in Mice

“…Exogenous administration of sublethal doses of TNF-· that do not cause signifi-320 Neuroimmunomodulation 1999; 6:319-329 Ando/Dunn cant hemodynamic changes has been reported to exert CNS effects such as activation of the hypothalamic-pituitary-adrenal HPA axis [3][4][5], fever [6,7], increasing slowwave sleep [8], and reducing food intake [9]. TNF-· can induce taste aversions [9] and decrease social exploration [10], components of sickness behavior. TNF-· has been suggested to be one of the mediators of the actions of endotoxin on the brain, such as HPA activation [11], and changes in body temperature [7].…”