Allan Rechtschaffen - US grants

The long-term goal of this research is to discover the function(s) of sleep. This knowledge would help to understand the role of sleep loss in illness, the role of sleep in recovery, and proper sleep hygiene. The function could be revealed in the effects of sleep deprivation. Chronically sleep deprived rats show a stereotypic syndrome: weight loss in spite of increased food intake, skin pathology, increased plasma norepinephrine, decreased plasma thyroxin (but increased conversion to its active form), a decline in body temperature, and eventual death. Two pathological processes could mediate many of these symptoms--excessive energy expenditure and excessive heat loss. The first could be compensatory for the second. Proposed studies will evaluate putative mediators of the syndrome. To evaluate whether sympathetic activation mediates excess energy expenditure, effects of sympathetic blockade on development of the syndrome will be determined. To evaluate whether the thyroid system mediates excess energy expenditure, the effect of blocking thyroxin synthesis on development of the syndrome will be determined. If either procedure blocks increases in energy expenditure but hastens the temperature decline, then excess energy expenditure would emerge as a secondary symptom which compensates for excessive heat loss. To evaluate whether an unknown bloodborne calorigenic substance mediates the increased energy expenditure, the blood of sleep deprived rats will be circulated through selected organs of recipient rats while metabolic rate in these organs is measured. To evaluate whether sleep deprivation causes excessive heat loss, sleep deprived rats and their yoked controls will be compared on behavioral thermoregulation (excessive heat loss should increase heat-seeking behavior); body temperature response to heat and cold exposure (excessive heat loss should cause a relatively large decrease in the cold); and the coupling of peritoneal and hypothalamic temperatures (excessive heat loss would likely cause larger declines in peritoneal than in hypothalamic temperature). These studies would also indicate whether central or peripheral failures mediated any excessive heat loss.

The long-term objective is to discover the function(s) of sleep. Rats chronically sleep deprived by brief, forced locomotion at sleep onset have shown an increased thermoregulatory setpoint (leading to an early increase in body temperature), excessive heat loss (leading to a later decline in body temperature), and hormonal changes and increased metabolism appropriate to compensatory thermogenesis. Rats died after an average of 2.5 weeks of sleep deprivation. Yoked control rats which received the same stimulation, but randomly with respect to sleep, showed only minor effects. The aims of the proposed research are as follows. 1. To determine whether the deaths of sleep deprived rats are caused by their excessive heat loss, their body temperatures will be incubator-regulated to near normal. Survival times and sleep deprivation symptoms will be compared to those of sleep deprived rats maintained at a constant, "normal" ambient temperature. 2. To determine whether self-controlled body temperatures prolong survival during sleep deprivation, rats will be provided with operant control of ambient temperature. Body temperature, survival time, and symptoms of sleep deprivation will be compared with those of yoked controls and sleep deprived rats without operant temperature control. 3. To determine whether increased metabolism or other effects of hyperthyroidism increase or decrease survival and other symptoms, thyroxine will be chronically administered to sleep deprived rats. Survival times and sleep deprivation symptoms will be compared with those of yoked hyperthyroid control rats and euthyroid sleep deprived rats. 4. To determine whether the increased thermoregulatory setpoint of sleep deprived rats is mediated by prostaglandins and/or opioids, they will be given aspirin or naltrexone to determine whether either reverses the increase in body temperature which occurs early in sleep deprivation. 5. To determine whether sleep deprivation causes a desensitization or downregulation of central adrenoreceptors, regional brain adrenoreceptor number and affinity will be compared in sleep deprived rats, yoked control rats, and normally maintained rats. 6. To evaluate whether a need for paradoxical (REM) sleep is associated with low thermal resistance, rat strains with high and low amounts of paradoxical sleep will be compared on thermal resistance. Elucidation of the function of sleep could have important implications for human disorders of insomnia and hypersomnia, for efficient and healthy sleep hygiene, and for defining sleep requirements.

The long-term goal of this research is to discover the function(s) of sleep. This knowledge would help to understand the role of sleep loss in illness, the role of sleep in recovery, and proper sleep hygiene. The function could be revealed in the effects of sleep deprivation. Chronically sleep deprived rats show a stereotypic syndrome: weight loss in spite of increased food intake, skin pathology, increased plasma norepinephrine, decreased plasma thyroxin (but increased conversion to its active form), a decline in body temperature, and eventual death. Two pathological processes could mediate many of these symptoms--excessive energy expenditure and excessive heat loss. The first could be compensatory for the second. Proposed studies will evaluate putative mediators of the syndrome. To evaluate whether sympathetic activation mediates excess energy expenditure, effects of sympathetic blockade on development of the syndrome will be determined. To evaluate whether the thyroid system mediates excess energy expenditure, the effect of blocking thyroxin synthesis on development of the syndrome will be determined. If either procedure blocks increases in energy expenditure but hastens the temperature decline, then excess energy expenditure would emerge as a secondary symptom which compensates for excessive heat loss. To evaluate whether an unknown bloodborne calorigenic substance mediates the increased energy expenditure, the blood of sleep deprived rats will be circulated through selected organs of recipient rats while metabolic rate in these organs is measured. To evaluate whether sleep deprivation causes excessive heat loss, sleep deprived rats and their yoked controls will be compared on behavioral thermoregulation (excessive heat loss should increase heat-seeking behavior); body temperature response to heat and cold exposure (excessive heat loss should cause a relatively large decrease in the cold); and the coupling of peritoneal and hypothalamic temperatures (excessive heat loss would likely cause larger declines in peritoneal than in hypothalamic temperature). These studies would also indicate whether central or peripheral failures mediated any excessive heat loss.