A basic goal of this project is to analyze in detail, using automated procedures, the natural patterns of food intake and appetite of undisturbed, freely behaving rats. Utilizing a variety of procedures, we then propose to investigate the neurochemical substrates of these natural patterns, with the ultimate goal of relating these findings to neurochemical disturbances seen in clinical eating disorders. Previous studies have demonstrated that animals have the ability to select appropriate macronutrients in response to physiological signals. Moreover, evidence is now emerging to suggest the involvement and interaction of hypothalamic neurotransmitters in this process. The focus of this research is on alpha-noradrenergic and serotonergic systems in the brain. Specifically, we propose to investigate the hypothesis that norepinephrine and serotnoin in the medial hypothalamus have antagonistic effects in the control of carbohydrate ingestion, particularly at the onset of the active cycle, with norepinephrine acting to enhance carbohydrate meals while suppressing protein intake, and serotonin producing precisely the opposite pattern of effects. For the first experiment of the research plan, we propose to monitor continuously the natural nocturnal patterns of macronutrient ingestion in intact, freely feeding rats. Through peripheral and central drug injections, Experiment 2 will provide a systematic analysis of the impact of exogenous hypothalamic noradrenergic and serotonergic stimulation on nocturnal patterns of ingestion. The basic hypothesis will then be tested directly in Experiment 3, which via microdialysis and HPLC procedures, will measure endogenous hypothalamic release of norepinephrine and serotonin simultaneous to continuous measures of macronutrient intake. To understand the essential role of these neurotransmitters in normal feeding behavior, we will examine in Experiment 4, via hypothalamic neurotoxin injections, the impact of a relatively selective depletion of endogenous norepinephrine and serotonin, on temporal patterns of macronutrient intake, and in Experiment 5, we will similarly analyze the involvement of the adrenal hormone corticosterone, which is known to interact with hypothalamic monoamine systems, Finally, Experiment 6 will test, through brief exposures to food deprivation, the rats' patterns of compensatory feeding, in relation to normal and manipulated patterns of hypothalamic neurotransmitter activity and circulating corticosterone levels.
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