Obesity is related to a variety of pathologic conditions that include cancer, heart disease, diabetes, and renal insufficiency, all of which can lead to an early death and poor quality of life. In Canada, the rate of obesity and the health and economic issues associated with this condition have reached alarming levels. While it is clear that there are genetic factors that are closely associated with obesity, environmental factors also play an important role the behavioral and physiological responses that lead to body weight alterations and ultimately in obesity and metabolic syndrome. Stress, for example has been associated with a number of metabolic changes that ultimately can lead to obesity, insulin resistance, and cardiovascular disease. Interestingly, a number of symptoms that are seen following exposure to different types of stressors are also seen in animals exposed to chronically elevated levels of the hormone ghrelin. Ghrelin, a stomach derived hormone, is commonly associated with the stimulation of appetite and food intake (particularly the intake of high calorie foods), as well as the accumulation of body fat. Ghrelin appears to be released following exposure to stressors, and produces many of the behavioral and metabolic alterations that are seen following chronic stress paradigms. This proposal is aimed at deciphering the mechanisms by which ghrelin does this, including the potential for drugs that block or reduce ghrelin secretion to attenuate the metabolic effects of chronic stress. The results from the proposed studies will lead to a better understanding of the hormonal mechanisms by which stress responses alter behavioral and metabolic processes.