SEROTONIN/DOPAMINE MEDIATION OF EARLY CANCER ANOREXIA

Upstate Medical University, Syracuse NY

Investigators

Linked publications & trials

Abstract

DESCRIPTION: 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.