Neural Substrates of Anorexia

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DESCRIPTION (provided by applicant): The goal of the project is to characterize the organization of central networks involved in anorexia. Anorexia is the loss of appetite, and is a serious complication that increases mortality in a number of human clinical conditions, including AIDS and cancer. Understanding the organization and interactions of circuits involved in generating and reversing anorexia will help us elucidate how these circuits function in both health and disease. Normally a state of negative energy balance elicits mechanisms to increase appetite and food intake. However, in anorexia these compensatory mechanisms fail. To accomplish the goal of this project, three experiments are proposed using a physiological model of anorexia resulting from dehydration (DE). DE-anorexia occurs after drinking hypertonic saline but is robustly reversed within minutes of returning access to drinking water. The experiments are: 1) To determine if DE inhibits eating in response to the orexigen Neuropeptide Y (NPY) when injected into the perifornical area of the lateral hypothalamus or the paraventricular nucleus of the hypothalamus; 2) An analysis of neuronal activation in NPY neurons immediately after anorexia reversal by using imunohistochemical detection of the phosphorylated form of p42/44 mitogen-activated protein/extracellular sinai-regulated kinase (pERK1/2) and in-situ hybridization for NPY mRNA; 3) To determine if low leptin levels are necessary for compensatory feeding after anorexia reversal by providing exogenous leptin to revent the decrease of circulating levels.