Innovations In Clinical Neuroscience

MAR-APR 2017

A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience

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Innovations in CLINICAL NEUROSCIENCE [ V O L U M E 1 4 , N U M B E R 3 – 4 , M A R C H – A P R I L 2 0 1 7 ] 34 was without effect on the prolactin response in their models. It is well established that secretion of prolactin concentrations are highest during sleep and lowest during wakefulness, 28 which suggests sleep and circadian rhythmicity interact in determining the temporal organization of prolactin secretion during the day. High prolactin level increase the duration and frequency of rapid eye movement (REM) sleep. The reduction in plasma prolactin with orexin administration may therefore be related to its effect on increasing arousal and reducing REM sleep. In their study, Chang et al 29 showed that rotating night shifts may cause high prolactin levels during the subsequent day, 29 which suggests a DORA administration at night may reduce plasma prolactin levels in the early morning and lead to an improvement of arousal and sleep. We could not add further support to this hypothesis in our study because most of our subjects received antipsychotics. Metabolic disorders. According to Schwartz et al, 30 glucose metabolism is regulated by both central and peripheral regulatory systems through their cooperative interactions. Funato 31 describes the daily rhythm of activated hypothalamic orexin as being controlled by the central biological clock located in suprachiasmatic nuclei, by blood glucose levels, and by brain signals that center around hunger/food-seeking behaviors. Acting through the sympathetic and parasympathetic nervous systems, the rhythmic activation of orexin helps to stabilize the sleep/wake cycle and modify hepatic glucose production and as well as enhance glucose consumption in skeletal muscles and thermogenesis in brown adipose tissue. 31–35 Orexin's role in modifying/reducing blood glucose is believed to be critical in the prevention of insulin resistance caused by age, obesity, and depression. 36 Currently, suvorexant is only approved for insomnia, and the effect this drug has on glucose metabolism remains to be proven. An early study reported that the orexin-1 receptor antagonist, SB-334867-A, exerted anti- obese and anti-diabetic effects when repetitively injected into genetically obese ob/ob mice at daytime for two weeks. 37 Through the enhancement of brown adipose tissue thermogenesis, SB-334867-A appears to reduce adiposity and increase energy expenditure. Moreover, the administration of SB-334867-A at the resting state may strengthen normal sleep/wake and feeding cycles, which can improve glucose metabolism in the liver and skeletal muscle. In our present study, the fasting insulin levels at Week 8 were decreased from baseline, although not significantly, which may indicate that suvorexant at the clinical dosage for insomnia has the potential to have an advantageous effect on several metabolic disorders. Mechanism of autonomic and neuroendocrine system. Orexin-A and orexin-B are endogenous neuropeptide agonist for orexin receptor-1 (OX 1 R) and orexin receptor-2 (OX 2 R). Orexin-A has equal affinity for OX 1 R and OX 2 R, whereas orexin-B displays higher affinity for OX 2 R. 2 FIGURE 1. Changes in the levels of prolactin, insulin, cortisol, noradrenaline, white blood cell count, and pulse rate at baseline and Weeks 4 and 8

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