Orexin/hypocretin neurons play a crucial role in the regulation of sleep/wakefulness, primarily in the maintenance of wakefulness. These neurons innervate wide areas of the brain and receive diverse synaptic inputs including those from serotonergic (5-HT) neurons in the raphe nucleus. Previously we showed that pharmacological application of 5-HT directly inhibited orexin neurons via 5-HT1A rece...

Previously, we reported that lateral hypothalamic (LH) orexin neurons are stimulated in proportion to the preference shown for reward-associated cues during conditioned place preference (CPP) testing. Here, we examine for the first time the role of these neurons in the acquisition of morphine CPP. Results show that LH orexin neurons, but not those in the perifornical area (PFA), are stimulated ...

The neuropeptides orexins and their G protein-coupled receptors, OX(1) and OX(2), were discovered in 1998, and since then, their role has been investigated in many functions mediated by the central nervous system, including sleep and wakefulness, appetite/metabolism, stress response, reward/addiction, and analgesia. Orexins also have peripheral actions of less clear physiological significance s...

BACKGROUND Orexins A and B (also named hypocretins 1 and 2) are hypothalamic peptides with pleiotropic activity. They signal through two G protein-coupled receptors: OX1R and OX2R. We have previously demonstrated that both types of orexin receptors are expressed in cultured rat cortical neurons, and stimulation of the predominant OX2R inhibits cyclic AMP synthesis. In the present work, we exami...

Orexin neuropeptides influence multiple homeostatic functions and play an essential role in the expression of normal sleep-wake behavior. While their two known receptors (OX1 and OX2) are targets for novel pharmacotherapeutics, the actions mediated by each receptor remain largely unexplored. Using brain slices from mice constitutively lacking either receptor, we used whole-cell and Ca(2+) imagi...

Obesity is a public health disease and its incidence is steadily increasing both in adults and in children especially in the Western World. It is important to understand the underlying mechanisms of obesity and possible treatments as the orexin system with its receptors, which are involved in different physiological processes. In fact, the aim of this mini-review is to consider the importance o...

Orexin receptor antagonists represent attractive targets for the development of drugs for the treatment of insomnia. Both efficacy and safety are crucial in clinical settings and thorough investigations of pharmacokinetics and pharmacodynamics can predict contributing factors such as duration of action and undesirable effects. To this end, we studied the interactions between various "dual" orex...

Close intra-arterial infusion of the appetite regulating peptide orexin-A stimulates bicarbonate secretion from the duodenal mucosa. The aim of the present study was to elucidate the ability of orexin-A to induce intracellular calcium signaling in acutely isolated duodenal enterocytes. Freshly isolated clusters of enterocytes, obtained from rat duodenal mucosa or human duodenal biopsies, were l...

Orexin, mainly produced by orexin-expressing neurons in the lateral hypothalamus (LH), plays an important role in pain modulation. Moreover, it is shown that the nucleus accumbens (NAc) is one of the important areas involved in this modulation. Orexin-1 (OX1) and orexin-2 (OX2) receptors are densely distributed in the NAc. The study investigated the involvement of OX1 receptors in the NAc on an...