HYPOCRETIN, HISTAMINE AND THE RESTLESS LEGS SYNDROME

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。不宁腿综合征（RLS）是一种与睡眠有关的感觉运动障碍，由休息和不活动引起，通过运动缓解。它包括一种强烈的移动腿的冲动。有强烈的昼夜节律模式，夜间症状加重，早晨明显缓解。尽管睡眠质量不佳，但RLS患者并没有表现出明显的白天嗜睡，尽管他们确实表现出疲劳。这表明睡眠脚动症可能涉及代偿性唤醒系统。下丘脑分泌素可能是RLS中介导觉醒的一个潜在候选物质。下丘脑泌素在未经治疗的RLS患者中被发现升高，特别是在早发性RLS患者中（症状在45岁之前开始）。已知下丘脑分泌素系统通过作用于组胺系统来诱导觉醒。值得注意的是，有一些RLS患者的轶事报道称，抗组胺药会加剧RLS的症状。本研究的目的是检验以下假设：1)抗组胺药物苯海拉明比镇静剂量的劳拉西泮更能诱发睡眠倒睡症状（PLMW和主观报告的症状）；2)相对于晚发性RLS患者，早发性RLS患者服用苯海拉明后，RLS症状的增加幅度更大；3)与先前报道的未治疗的RLS患者相比，目前接受治疗的RLS患者夜间脑脊液下丘脑泌素/食欲素水平较低；4)在目前接受多巴胺能药物治疗的RLS患者中，脑脊液下丘脑分泌素与警觉性指标直接相关，与嗜睡指标呈负相关。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Restless Legs Syndrome (RLS) is a sleep-related, sensori-motor disorder brought on by rest and inactivity and relieved by movement. It involves a compelling urge to move the legs. There is a strong circadian pattern, with symptoms becoming worse at night with marked relief by morning. Despite poor sleep, RLS patients do not report significant daytime sleepiness, although they do report fatigue. This would suggest that RLS may involve a compensatory arousal system. One potential candidate that may mediate arousal in RLS is hypocretin. Hypocretin has been found to be elevated in untreated patients with RLS, particularly in patients with early-onset RLS (in which symptoms begin before age 45). The hypocretin system is known to induce arousal by its actions on the histamine system. Notably, there are anecdotal reports by some patients with RLS that anti-histamines exacerbate the symptoms of RLS. The purpose of this study is to test the following hypotheses: 1) The antihistamine drug, benadryl, will induce RLS symptoms (PLMW and subjective reports of symptoms) significantly more than a sedating dose of lorazepam; 2) The increase in RLS symptoms following Benadryl will be greater for early-onset RLS patients, relative to late-onset RLS patients; 3) Nocturnal CSF of hypocretin/orexin will be lower on patients currently under treatment for RLS than those previously reported in un-treated RLS; 4) In RLS patients currently being treated with dopaminergic medication, CSF hypocretin will correlate directly with measures of alertness and inversely with measures of sleepiness.