Orexins

Mood and hedonic value associated with feeding, food intake, foraging, consummatory behaviors, and craving in addiction complex regulation by food entrainable oscillators in the brain and periphery, neuropeptides (including orexins) and biogenic amines. 

Orexins Appetite Control Anti-obesity Drugs... 

Lesions of the lateral hypothalamic area (LHA) cause anorexia, whereas ablation of the paraventricular nucleus (PVN) cause a hyperphagic obesity syndrome. Consistent with these results, LHA neurons express the orexigenic neuropeptides MCH and orexin. PVN neurons produce several neuropeptides that are anorex-igenic when administered directly into the brain (CRH, TRH, oxytocin), in addition to their better known roles as endocrine regulators. LHA and PVN receive rich inputs from axons of NPY/AgRP and aMSH/CART-producing neurons in the arcuate nucleus. 

Hypothalamus-pituitary-adrenal (HPA) Axis Circadian Rhythms Appetite Control Orexins... 

The lateral hypothalamic area has been identified as a feeding centre by studies involving electric stimulation and discrete lesions. Neurons in the lateral hypothalamic area and the neighbouring perifornical area express neuropeptides that stimulate feeding when injected into cerebral ventricles (orexins 1 and 2, melanin-concentrating hormone (MCH)). 

Orexin A (OX-A) and Orexin-B (OX-B) Hypocretin-1 (Hcttl) and Hypocretin-2 (Hcrt2)... 

In the mammalian brain orexins are almost exclusively expressed in a small group of neurons located in the lateral hypothalamus (LH) andperifornical area (PEA)... 

Major efferent projections of the hypothalamic orexin system comprise descending and ascending, dorsal and ventral pathways that terminate preferentially in aminergic, endocrine, and autonomic control centers in the hypothalamus, midbrain, brainstem, and spinal cord, as well as in limbic cortical and subcortical structures, including sqDtum, amygdala, thalamus,... 

The diffuse nature of orexinergic projections is consistent with combined patterns of expression of the two orexin receptors, which is widespread but differential and often complementary within and even outside the CNS. OX2Rs are found primarily in structures attributed to control of sleq)-wake functions, whereas OXIRs are more abundant in limbic structures controlling aspects of feeding, autonomic outflow, energy homeostasis, and to a lesser extent also REM-sleq). 

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