Our research is focused on determining the causes of physiological disturbances which result from sleep loss. Our results indicate: 1. Sleep deprived rats utilize food and body energy stores at an accelerated, unhealthy rate and become debilitated. Metabolism is not down-regulated to compensate for this negative energy balance as would be expected if deprived rats were, functionally, starving. 2. Prolonged sleep loss in rats causes symptoms resembling protein malnutrition. We determined that proteins need not be used simply to supply caloric requirements of a high energy expenditure during sleep loss and that hypoalbuminemia (the hallmark of protein malnutrition) is only a secondary pathogenic factor during sleep loss. 3. Thyroid hormones are implicated in the metabolic and thermoregulatory alterations during sleep loss. To assess whether brain stimulation of the thyroid could be responsible for the altered plasma hormonal levels during sleep loss, we tested the release of thyroid-stimulating hormone from the pituitary. The results indicate that the brain is functioning as if the periphery is euthyroid; pituitary responses are neither exaggerated nor blunted. We are currently investigating possible causes of altered plasma T3 and T4 levels by peripheral mechanisms. 4. Thermoregulation is widely believed to be suspended during rapid-eye-movement (REM) sleep. Our data, however, indicate that brain temperature increases during rapid-eye-movement sleep may reverse brain temperature declines during previous slow wave sleep. REM sleep may have a thermoregulatory role in keeping the brain temperature within a narrow range during the sleep period. We are broadening our understanding of the consequences of sleep loss on the brain by measuring regional energy use and neurochemical changes. We developed a method of chronic arterial and venous catheterization to conduct brain metabolism studies after prolonged sleep loss and recovery sleep. Densitometry analysis and sample collection for neurochemical analysis is ongoing. The significance of this work lies in our providing basic biological knowledge about how and why sleep occurs and what harm is caused by sleep loss. We may be able to determine how and why sleep is necessary for health by tracing mechanisms and causes of the sleep loss pathology.