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.
Laviano
A
A
Department of Surgery, University Hospital, SUNY Health Science Center, Syracuse, USA.
Gleason
J R
JR
Meguid
M M
MM
Yang
Z J
ZJ
Cangiano
C
C
Rossi Fanelli
F
F
D000818:Animals; D000855:Anorexia / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D004435:Eating / Q000187:drug effects / Q000502:physiology; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D008803:Mianserin / Q000008:administration & dosage*; D051381:Rats; D011916:Rats, Inbred F344; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D012513:Sarcoma, Experimental / Q000150:complications*; D012702:Serotonin Antagonists / Q000008:administration & dosage; D012795:Sialoglycoproteins / Q000008:administration & dosage*; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects
D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D012702:Serotonin Antagonists; D012795:Sialoglycoproteins; D008803:Mianserin