Orexin A activates locus coeruleus cell firing and increases arousal in the rat

The localization of orexin neuropeptides in the lateral hypothalamus has fo cused interest on their role in ingestion. The orexigenic neurones in the l ateral hypothalamus, however, project widely in the brain, and thus the phy siological role of orexins is likely to be complex. Here we describe an inv estigation of the action of orexin A in modulating the arousal state of rat s by using a combination of tissue localization and electrophysiological an d behavioral techniques. We show that the brain region receiving the denses t innervation from orexinergic nerves is the locus coeruleus, a key modulat or of attentional state, where application of orexin A increases cell firin g of intrinsic noradrenergic neurones. Orexin A increases arousal and locom otor activity and modulates neuroendocrine function. The data suggest that orexin A plays an Important role in orchestrating the sleep-wake cycle.