HYPOCRETIN, HISTAMINE AND THE RESTLESS LEGS SYNDROME

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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 brough on by rest and inactivity and relived 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.