The finding of orexin/hypocretin deficiency in narcolepsy patients suggests that this hypothalamic neuropeptide plays a crucial role in regulating sleep/wakefulness states. However, very little is known about the synaptic input of orexin/hypocretin-producing neurons (orexin neurons). We applied a transgenic method to map upstream neuronal populations that have synaptic connections to orexin neu...

Introduction: Orexin-A and B (Hypocretin 1 and 2) are neuropeptides that are mostly expressed in the posterior and lateral hypothalamus (LH). Intracisternal (ICV) and intratechal (IT) injections of orexin-A (hypocretin-1) have been shown to elicit analgesic responses in formalin test. However, the locations of central sites that may mediate these effects have not been clearly elucidated. Ore...

Hypocretin/orexin acts pharmacologically in the hypothalamus to stimulate stress hormone secretion at least in part by an action in the hypothalamic paraventricular nucleus, where the peptide's receptors have been localized. In addition, orexin acts in the brain to increase sympathetic tone and, therefore, mean arterial pressure and heart rate. We provide evidence for the role of endogenously p...

Two experiments used vivo morpholinos to assess the role of orexin/hypocretin in ABA renewal of extinguished alcohol seeking. Rats were trained to respond for alcoholic beer in a distinctive context, A, and then extinguished in a second distinctive context, B. When rats were tested in the extinction context, ABB, responding was low but when they were tested in the training context, ABA, respond...

Hypocretins/orexins are primary excitatory neuropeptides located exclusively in neurons of the lateral hypothalamic area, which send projections to most monoaminergic nuclei. It has been reported that i.c.v. injection of hypocretin 1 (orexin A) enhances wakefulness in rats and mice. The present work was carried out to examine the roles of hypocretins in nociception in mice. The presence of robu...

In mammals Orexin-A and -B are neuropeptides involved in the hypothalamic regulation of diverse physiological functions including food intake and the sleep-wake cycle. This generalisation was investigated in meat-(broiler) and layer-type juvenile domestic chickens by immunocytochemical localisation of orexin A/B in the hypothalamus, and by measurements of hypothalamic hypocretin mRNA which enco...

Orexin receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on [43]) are activated endogenous polypeptides orexin-A and orexin-B (also known hypocretin-1 -2; 33 28 aa) derived from a common precursor, preproorexin or orexin proteolytic cleavage some typical peptide modifications [117]. signaling has been associated with regulation of sleep wakefulness, reward addiction, appetite feed...

Hypocretin/orexin is produced exclusively in the dorsal and lateral hypothalamus but its projection is widespread within the brain and plays important roles. In this paper, we review the independent discoveries of the hypocretin/orexin peptides, the neuroanatomy of this system, and the link to the sleep disorder narcolepsy that has led to the idea that this system plays a crucial role in the re...

Recent studies have implicated the hypocretin/orexinergic system in reward-seeking behavior. Almorexant, a dual orexin/hypocretin R(1) and R(2) receptor antagonist, has proven effective in preclinical studies in promoting sleep in animal models and was in Phase III clinical trials for sleep disorders. The present study combines behavioral assays with in vitro biochemical and electrophysiologica...