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.

Fig. 1.

Representative neurogram from 1 subject during baseline and head-down rotation (HDR) after the ingestion of placebo or melatonin. Muscle sympathetic nerve activity (MSNA) total activity is indicated above each recording. au, arbitrary units.

Fig. 2.

MSNA (total activity and burst frequency) responses to HDR with and without melatonin ingestion. MSNA responses to HDR were significantly attenuated with melatonin. *Significantly different from placebo: P < 0.05.

Fig. 3.

Representative averaged vestibular evoked myogenic potential (VEMP) waveforms from 1 subject before and after the ingestion of melatonin. p13 and n23 are first nadir and first peak respectively.

Fig. 4.

p13-n23 interpeak amplitudes for melatonin and placebo groups. Melatonin did not alter the interpeak amplitudes. The interpeak amplitudes measured from the placebo group were comparable to the melatonin group (time × group interaction: P = 0.91).