Effects of lateral preoptic area application of orexin-A on sleep-wakefulness

Deficiency of orexin, a newly discovered hypothalamic peptide, is thought t o lead to abnormal sleepiness and cataplexy in both human narcolepsy and an imal models of the disease. As the POA contains extensive orexin terminals and is established as a sleep/arousal regulatory site, we evaluated a hypot hesis that this site is a target for the arousal-inducing effects of orexin . Orexin-A was microinjected into lateral preoptic area (IPOA) and the effe cts on sleep-wakefulness and brain temperature were studied. Compared to sa line vehicle control, orexin-A induced an increase in wakefulness for 70 mi n and suppressed all sleep stages, especially SWS2 and REM for 80 and 90 mi n, respectively. Brain temperature was not differentially affected by orexi n-A compared to saline control. The orexin-induced arousal and REM suppress ion are consistent with the orexin-deficiency model of narcolepsy. Our resu lts suggest that the IPOA orexin terminal field or adjacent structures may be a locus of arousal regulation by this peptide and a substrate of sleep-w ake regulatory deficits in:narcolepsy. NeuroReport 11:3423-3426 (C) 2000 Li ppincott Williams & Wilkins.