Our objective is to establish the relationship between Interleukin-1 (IL-1) (also called endogenous pyrogen) and the regulation of sleep-wake cycles. The fundamental proposition that underlies this concern is that there is an endogenous factor(s) that modulates sleep-wake cycles. We hypothesize that IL-1 is one of these substances. An obvious prerequisite to this hypothesis is to show that IL-1 induces sleep. Preliminary results from our laboratory show that IL-1 induces dose-dependent increases in rabbit slow-wave sleep (SWS) and that these sleep responses are independent from febrile responses that are also induced by IL-1. In these studies we used rabbits whic do not have pronounced circadian sleep-wake cycles and restricted our analysis to SWS. We now propose to determine the effects of IL-1 on the architecture of sleep-wake cycles using cats. Our studies in cats will also employ antipyretics to determine if, as in rabbits, febrile responses can be separated from sleep responses. These studies will be carried out using cats with chronically implanted EEG, and EMG electrodes, brain thermistors and ventricular guide tubes. Following intraventricular infusion of various doses of IL-1, responses will be monitored for 32 hours. The effects of IL-1 on brain temperature, SWS and REM sleep as well as the relationship of these responses to each other and wakefulness will be determined. We also propose to microinject IL-1 into brain to determine the effective site(s) responsible for sleep responses. In this case rabbits will be provided with chronically implanted EEG electrodes, brain thermistors, and brain guide tubes. Following injections of 1-2 ul of solutions of IL-1, rabbits will be recorded from for 6 or more hours. During this period duration of SWS, brain temperature and quantitative changes in EEG slow waves will be determined. Anticipated results are of broad significance since IL-1 may provide a new endogenous agent that can be used to examine the mechanisms that underlie sleep.
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