This proposal addresses the neuropharmacology of human feeding behavior, testing the general hypothesis that aspects of food intake measured over extended time periods under controlled, but relatively naturalistic living conditions, can be functionally related to serotonergic neurochemical systems. In addition, it is proposed that the functional interactions between central serotonergic events and the topography of human feeding behavior can productively be analyzed within a framework emphasizing repeated observations on single subjects under varying feeding conditions. Dose-response functions of changes in eating behavior for a number of agents affecting serotonergic systems will be determined under conditions in which the caloric content of a lunch meal will also be systematically manipulated. Changes in the caloric content of the lunch meal will be accomplished by specifically altering the carbohydrate content, and maintaining stable levels of other macronutrients. Specifically, the present proposal is designed to test the following hypotheses: 1) Substances that increase the amount of serotonin in synapses decrease food intake by decreasing the size of eating occasions. 2) Serotonin-2 antagonists increase food intake by increasing the size of eating occasions. 3) Serotonin-la agonists also increase food intake by increasing the size of eating occasions. In the case of these serotonergic drugs there will be an interaction between drug and the carbohydrate content of the lunch meal. 4) Substances that increase the amount of dopamine in synapses decrease food intake by decreasing the number of eating occasions regardless of the carbohydrate content of the lunch meal. 5) In the absence of changes in body weight, the serotonergic drugs will have effects on feeding topography during repeated administration similar to those observed following acute administration of these compounds. The analysis of changes in feeding behavior in response to the administration of a number of agents affecting serotonin under a wide range of conditions will provide vital information about the influence of serotonergic systems in determining feeding behavior. Additionally, this research will provide a theoretical framework and experimental methodology for further research on the neuropharmacology of human feeding behavior.
