Physiological Role of Orexin/Hypocretin in the Human Body in Motivated Behavior: A Comprehensive Review

Neurohormones are neurosecretory materials released by neurosecretory cells that serve both as neuromodulators in the brain and spinal cord and as circulating regulatory hormones. They serve a wide range of functions, including homeostasis, development, and modulation of neuronal and muscle activity. In the hypothalamus, neurohormones called hypocretins are created that were discovered in the late nineties. Orexin receptors (OXRs) have been shown to enhance synaptic signaling in the central nervous system at the cellular level. The orexins improve stimulated neural activity in the hippocampus, which, in turn, aids with spatial memory, learning, and mood. They present themselves as mediators for the hypothalamic functions. They have been shown to regulate sleep-wake cycles, arousal mechanisms, addiction, sympathetic nerve activity (SNA), blood pressure, and thermogenesis. Its role in storing brown adipose tissue has implications for thermal homeostasis. The significant role of orexins is seen in tumorigenesis when orexin A (OrxA) and orexin B (OrxB) induce apoptosis in fast-growing tumor cells. Orexin-null subjects show clinical narcolepsy, indicating that orexins were responsible for keeping them awake. Orexin microinjections in mice brains stimulated increased physical activity, thus possibly countering diet-induced obesity. Physical activity significantly increased plasma orexin-A levels, which facilitated the process of energy homeostasis. The amount of adrenocorticotropic hormone (ACTH) increases in stress conditions, which further facilitates the release of the stress hormone cortisol. No increase in the ACTH hormone is seen in stressed mice administered with orexin receptor 2 (OX2R) antagonists thus showing orexin's role in stress reaction. As a result of linking hypocretin/orexin to various physiological procedures, increased research into the medicinal potential of drugs targeting these receptors is emerging. We summed up in this review the recent advances in our understanding of how orexin and its receptor system play an essential role in clinical and pathological functions. This research summarizes a new area for research in human medicine, providing the possibility of controlling a vast array of physiological functions through intra-cerebroventricular injections of a single neuropeptide.