Effects of intra-VMN mianserin and IL-1ra on meal number in anorectic tumor-bearing rats

Background: Tumor growth in animals and humans is associated with the onset of anorexia and reduced food intake. We previously demonstrated that the ventromedial nucleus of hypothalamus (VMN) plays a contributory role in mediating cancer anorexia, Because serotonin and interleukin-1 (IL-1) are putative mediators of cancer anorexia. we hypothesized that their influence on food intake during tumor growth might occur via their action within the VMN. Methods: To test this hypothesis, 12 Fischer rats injected subcutaneously with 10(6) viable MCA sarcoma cells (TB rats) and their nontumor-bearing controls (NTB, n=13) were studied. When anorexia developed, TB and NTB rats received bilateral intra-VMN microinjections of the serotonin antagonist mianserin (200 nmol) or the IL-1 receptor antagonist (IL-1ra, 25 ng), Food intake and its determinants of meal number and size were continuously recorded via a computerized device. Results: In NTB rats, intra-VMN mianserin did not affect food intake, whereas after IL-1ra or vehicle a momentary decrease in food intake due to a predominant reduction of meal size occurred. In TB rats, intra-VMN mianserin or IL-1ra selectively increased meal number, leading to improved food intake. Conclusions: Data suggest that intra-VMN serotonin and IL-1 are involved in influencing cancer related anorexia.