title: Melatonin attenuates the vestibulosympathetic but not vestibulocollic reflexes in humans: selective impairment of the utricles.
abstract: Melatonin has been reported to decrease nerve activity of medial vestibular nuclei in the rat and is associated with attenuated muscle sympathetic nerve activity (MSNA) responses to baroreceptor unloading in humans. The purpose of this study was to determine if melatonin alters the vestibulosympathetic reflex (VSR) and vestibulocollic reflex (VCR) in humans. In study 1, MSNA, arterial blood pressure, and heart rate were measured in 12 healthy subjects (28 ± 1 yr; 6 men, 6 women) during head-down rotation (HDR) before and 45 min after ingestion of either melatonin (3 mg) or placebo (sucrose). Subjects returned at least 2 days later at the same time of day to repeat the trial after ingesting the opposite treatment (melatonin or placebo). Melatonin significantly attenuated MSNA responses during HDR compared with placebo (burst frequency Δ 4 ± 1 vs. Δ 7 ± 1 bursts/min, and total MSNA Δ 51 ± 20 and Δ 96 ± 15%, respectively; P < 0.02). In study 2, vestibular evoked myogenic potentials (VEMP) were measured in 10 healthy subjects (26 ± 1 yr; 4 men and 6 women) before and after ingestion of 3 mg melatonin. Melatonin did not alter the timing of the p13 and n23 peaks (pre-melatonin 13.2 ± 0.4 and 21.3 ± 0.6 ms vs. post-melatonin 13.5 ± 0.4 and 21.4 ± 0.7 ms, respectively) or the p13-n23 interpeak amplitudes [pre-melatonin 22.5 ± 4.6 arbitrary units (au) and post-melatonin 22.7 ± 4.6 au]. In summary, melatonin attenuates the VSR and supports the concept that melatonin negatively affects orthostatic tolerance. However, melatonin does not alter the VCR in humans suggesting melatonin's effect on the VSR appears to be mediated by the utricles.
authors.affiliation: Department of Cellular and Molecular Physiology, General Clinical Research Center, Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033-2390, USA.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Cook
authors.forename: Chester A
authors.initials: CA
authors.lastname: Ray
mesh_terms: D000161:Acoustic Stimulation; D000328:Adult; D017704:Baroreflex / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004576:Electromyography; D005260:Female; D018475:Head-Down Tilt; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008550:Melatonin / Q000008:administration & dosage*; D054971:Orthostatic Intolerance / Q000503:physiopathology / Q000517:prevention & control*; D015990:Placebo Effect; D011930:Reaction Time; D012399:Rotation; D012444:Saccule and Utricle / Q000294:innervation*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D013997:Time Factors; D058585:Vestibular Evoked Myogenic Potentials / Q000187:drug effects; D014725:Vestibular Nerve / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D008550:Melatonin