The long-term objective of this revised new application is to more fully understand food intake (FI) control in normals and disease states, the investigators propose studying serotonin (5-HT) and dopamine (DA) mediation of IL-1 induced early cancer anorexia in a rat MCA tumor model. In the studies the investigators will use: 1) a rat eater meter to measure FI, meal number (MN) and size (MZ) in free-feeding tumor bearing and control rats; 2) microdialysis of ventromedial hypothalamic nucleus (VMN) and lateral hypothalamic area (LHA) to examine concentrations of biogenic amines; and 3) stereotactic micro injections of neurotransmitter antagonists/agonists in VMN and LHA. In tumor-bearing rats, the investigators propose to determine if early cancer anorexia is: 1) associated with VMN and LHA by blocking their activity via micro injections to increase FI; and 2) mediated by increased VMN 5-HT/DA as measured by microdialysis. The investigators propose to increase FI by modulating VMN/LHA serotonin through micro injections of either a serotonin antagonist, DA agonist, and IL-1ra. While delineating the serotonergic-dopaminergic parameters of early anorexia in tumor-bearing rats, the investigators will induce in normal rats external perturbations like those induced by the tumor, and assess the effects of those on the same serotonergic/dopaminergic parameters measured in tumor-bearing rats, i.e., VMN/LHA microdialysis and blocking agent micro injections. As external perturbations, they will use progressively increasing peripheral infusions of IL-1 and TRP, the serotonin precursor, as would result from a progressively growing tumor.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA070239-04
Application #
6173545
Study Section
Metabolic Pathology Study Section (MEP)
Program Officer
Xie, Heng
Project Start
1997-07-15
Project End
2002-04-30
Budget Start
2000-05-25
Budget End
2001-04-30
Support Year
4
Fiscal Year
2000
Total Cost
$219,247
Indirect Cost
Name
Upstate Medical University
Department
Surgery
Type
Schools of Medicine
DUNS #
058889106
City
Syracuse
State
NY
Country
United States
Zip Code
13210
Guijarro, Ana; Laviano, Alessandro; Meguid, Michael M (2006) Hypothalamic integration of immune function and metabolism. Prog Brain Res 153:367-405
Goncalves, Carolina G; Ramos, Eduardo J B; Romanova, Irina V et al. (2006) Omega-3 fatty acids improve appetite in cancer anorexia, but tumor resecting restores it. Surgery 139:202-8
Ramos, Eduardo J B; Romanova, Irina V; Suzuki, Susumu et al. (2005) Effects of omega-3 fatty acids on orexigenic and anorexigenic modulators at the onset of anorexia. Brain Res 1046:157-64
Turrin, Nicolas P; Ilyin, Sergey E; Gayle, Dave A et al. (2004) Interleukin-1beta system in anorectic catabolic tumor-bearing rats. Curr Opin Clin Nutr Metab Care 7:419-26
Romanova, Irina V; Ramos, Eduardo J B; Xu, Yuan et al. (2004) Neurobiologic changes in the hypothalamus associated with weight loss after gastric bypass. J Am Coll Surg 199:887-95
Sato, T; Laviano, A; Meguid, M M et al. (2003) Involvement of plasma leptin, insulin and free tryptophan in cytokine-induced anorexia. Clin Nutr 22:139-46
Nandi, Jyotirmoy; Meguid, Michael M; Inui, Akio et al. (2002) Central mechanisms involved with catabolism. Curr Opin Clin Nutr Metab Care 5:407-18
Sato, T; Fetissov, S O; Meguid, M M et al. (2001) Intra-supraoptic nucleus sulpiride improves anorexia in tumor-bearing rats. Neuroreport 12:2429-32
Sato, T; Meguid, M M; Fetissov, S O et al. (2001) Hypothalamic dopaminergic receptor expressions in anorexia of tumor-bearing rats. Am J Physiol Regul Integr Comp Physiol 281:R1907-16
Meguid, M M; Fetissov, S O; Varma, M et al. (2000) Hypothalamic dopamine and serotonin in the regulation of food intake. Nutrition 16:843-57