HYPOCRETIN, HISTAMINE AND THE RESTLESS LEGS SYNDROME

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。不宁腿综合征（RLS）是一种睡眠相关的感觉运动障碍，由休息和不活动引起，运动缓解。它包括一种强烈的冲动去移动腿。有一个强烈的昼夜节律模式，症状在晚上变得更糟，到早上明显缓解。尽管睡眠不好，RLS患者并没有报告明显的白天嗜睡，尽管他们确实报告疲劳。这表明RLS可能涉及一种补偿性唤醒系统。一个可能在RLS中介导唤醒的潜在候选者是下丘脑泌素。已经发现在未经治疗的RLS患者中，特别是在早发性RLS患者（其中症状开始于45岁之前）中，下丘脑泌素升高。已知下丘脑泌素系统通过其对组胺系统的作用来诱导唤醒。值得注意的是，有一些RLS患者的轶事报告称，抗组胺药会加重RLS的症状。本研究的目的是检验以下假设：1）抗组胺药苯那君会诱发RLS症状（PLMW和症状的主观报告）显著多于镇静剂量的劳拉西泮; 2）相对于晚发性RLS患者，对于早发性RLS患者，苯那君后RLS症状的增加将更大; 3）目前正在治疗RLS的患者的下丘脑泌素/食欲素的夜间CSF将低于先前在未治疗的RLS中报道的那些; 4）在目前正在用多巴胺能药物治疗的RLS患者中，CSF下丘脑泌素将与警觉性的测量直接相关，与嗜睡的测量相反。

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.