Neuropeptides and Cancer Anorexia

Several approaches have been used to study the role of neuropeptides in the regulation of eating behaviour, including various animal models (e.g. transgenic animals and gene-deletion models) and physiological studies evaluating the response of cannulated tumour-bearing animals to intracere-broventricular or hypothalamic intranuclear injection of peptides and monoamines. Although these studies provide further insight into the role of dif-

Fig. 7. Food intake in tumour-bearing rats (TB-R) and control groups before and after tumour resection and sham operation, respectively. In the TB-R group, food intake decreased with the onset of anorexia. When rats were defined as anorectic, tumours were resected, while their controls underwent sham operation. Food intake continued to be measured until it normalised in TB-R, at which time rats in both groups were killed to harvest their brains. (From [59])

Fig. 7. Food intake in tumour-bearing rats (TB-R) and control groups before and after tumour resection and sham operation, respectively. In the TB-R group, food intake decreased with the onset of anorexia. When rats were defined as anorectic, tumours were resected, while their controls underwent sham operation. Food intake continued to be measured until it normalised in TB-R, at which time rats in both groups were killed to harvest their brains. (From [59])

Fig.8. Immunocytochemical visualisation of serotonin (5-HT)iB receptors (a, b, e, f) and NPY immunoreactive fibers (c, d, g, h) in the hypothalamus of control and tumour-resected rats. SO, supraoptic; PVm, magnocellular part of paraventricular nucleus; PVp, parvocellular part of paraventricular nucleus; OC, optic chiasm; Bar, 100 |m. (From [59])

Fig.8. Immunocytochemical visualisation of serotonin (5-HT)iB receptors (a, b, e, f) and NPY immunoreactive fibers (c, d, g, h) in the hypothalamus of control and tumour-resected rats. SO, supraoptic; PVm, magnocellular part of paraventricular nucleus; PVp, parvocellular part of paraventricular nucleus; OC, optic chiasm; Bar, 100 |m. (From [59])

ferent neuropeptides in cancer anorexia-cachexia syndrome, our knowledge remains limited and fragmented, making difficult the development of targeted drug therapies for anorexia. Neuropeptides involved in cancer anorexia can be divided into orexigenic and anorexigenic. Among the anorexigenic peptides, hypothalamic a-MSH is thought to be of primary importance in the inhibition of feeding and body weight gain because it induces anorexia primarily via the type 4-melanocortin receptor (MC4-R). Stimulation of the hypothalamic MC4-R appears to integrate peripheral signals that lead to anorexia, weight loss, hypodipsia, and decreased locomotion during illness [60]. Central administration of MC4-R agonists inhibits energy intake, increases energy expenditure, and reduces body weight [62, 63], whereas administration of MC4-R antagonists leads to an increase in food intake. It has been reported that weight loss and hypophagia induced by sarcoma growth can be reversed and prevented by the administration of the endogenous MC3/MC4 antagonist, AgRP. The prevention of tumour-induced hypophagia with early and repeated AgRP injections resulted in maintenance of normal food intake (Fig. 9) [61].

30 7 -^AGH Flood ACSF food

30 7 -^AGH Flood ACSF food

5 10 15 20 Days Post Tumor Implant t t r-

5 10 15 20 Days Post Tumor Implant

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