Dysfunction of the hypocretin/orexin (Hcrt/Orx) peptide system is closely linked to the sleep disorder narcolepsy, suggesting that it is also central to the normal regulation of sleep and wakefulness. Indeed, Hcrt/Orx peptides produce long-lasting excitation of arousal-related neurons, including those in the laterodorsal tegmentum (LDT) and the dorsal raphe (DR), although the mechanisms underly...

Introduction: It has been shown that orexin peptides have a role in opioid withdrawal behaviors. Orexin-expressing neurons that are present in the hypothalamic nuclei send dense projections to the Locus Coeruleus (LC). Withdrawal syndrome is temporally associated with hyperactivity of LC neurons. However, LC neurons do not show withdrawalinduced hyperactivity in the brain slices from morphin...

Orexin neurons (hypocretin neurons) have a critical role in the regulation of sleep/wakefulness, especially in the maintenance of arousal. Here, we revealed that orexin neurons are directly and indirectly activated by orexin via the orexin 2 receptor (OX2R). Orexin B (1 μM) induced depolarization in orexin neurons, which was still observed in the presence of TTX (1 μM), AP-5 (50 μM), and CNQX (...

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...

The neuropeptides, orexin-A and orexin-B, have been demonstrated to have a physiological role in the regulation of food intake in mammals. The effects of human orexin-A and orexin-B intracerebroventricular (i.c.v.) injection on the feeding behavior of goldfish (Carassius auratus) were investigated. I.c.v. injection of orexin-A and orexin-B both caused a significant increase in appetite, as indi...

The hypocretin/orexins (Hcrts/ORXs) are peptides produced in neurons in the lateral hypothalamic area that project to neuroendocrine centers in the hypothalamus. Hcrt/ORX receptors are present in the hypothalamus and anterior pituitary gland. We examined the possibility that the Hcrts/ORXs, which we have demonstrated previously to act in the brain to stimulate sympathetic function, could alter ...

Spontaneous physical activity (SPA) describes activity outside of formal exercise and shows large interindividual variability. The hypothalamic orexin/hypocretin peptides are key regulators of SPA. Orexins drive SPA within multiple brain sites, including rostral lateral hypothalamus (LH) and nucleus accumbens shell (NAcSh). Rats with high basal SPA (high activity, HA) show higher orexin mRNA ex...

The ability to awaken from sleep in response to important stimuli is a critical feature of normal sleep, as is maintaining sleep continuity in the presence of irrelevant background noise. Dual orexin receptor antagonists (DORAs) effectively promote sleep across species by targeting the evolutionarily conserved wake-promoting orexin signaling pathway. This study in dogs investigated whether DORA...

objective(s):reduction of pharmacological effectiveness or tolerance appears following repeated administration of many analgesic drugs. we investigated tolerance to anti-nociceptive effects of orexin-a, an endogenous potent analgesic peptide using the hot-plate test.materials and methods:orexin-a was microinjected icv (intracerebroventricular) with an interval of 12 hr for 7 continuous days and...