The goal is to develop a novel class of sleep-enhancing compounds that, unlike all currently available hypnotics, stimulate slow-wave sleep (SWS), the deepest and most restorative stage of sleep. The plan is to develop structural analogs of a natural neuromodulator, which is a potent stimulant of SWS, and has a specific newly identified receptor system in the brain. The objective of this Phase I proposal is to develop and validate the rat as a rapid and cost effective animal model for screening the compounds with the most potent effects on SWS.
The specific aims are 1. To characterize in detail optimum dose and time of day corresponding to maximal effect on SWS. 2. To develop a stepwise biobehavioral assay to rapidly screen candidate compounds using simple, inexpensive and minimally invasive techniques in order to select only the most promising for the EEG study; 3. To test the biobehavioral screen and the EEG model using published analogs with known binding and sedative properties.
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