Alpha-melanocyte stimulating hormone and adrenocorticotropic hormone: an alternative approach when thinking about restless legs syndrome?

Alpha-melanocyte stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH) possess properties suggesting that they may be involved in the pathogenesis of restless legs syndrome (RLS). We sought to determine if alpha-MSH and ACTH when administered centrally in rat recapitulate features reminiscent of RLS: increased activity, sleep fragmentation, and periodic movements during sleep. Rats were instrumented with electroencephalography, electromyography, and intracerebral cannulae and recorded for the measurement of sleep, periodic movements, and behavior following intracerebroventricular administration of alpha-MSH, ACTH, or saline. Studied behavior included grooming, locomotion, and rearing during wake and limb movements during sleep. Vigilance states included active wake (AW), quiet wake (QW), slow wave sleep I (SWSI), slow wave sleep II (SWSII), and paradoxical sleep (PS). All rats received normal saline acting as their own controls. Different rats received alpha-MSH in doses of 0.05, 0.5, 1.0, 2.0, and 6.0 microg or ACTH in doses of 0.5, 1.0, and 2.0 microg. Administered alpha-MSH caused an increase in waking behavior and prolongation of sleep latency, while ACTH stimulated waking behavior and fragmented sleep, yielding more AW and less SWSII and PS. Both hormones increased periodic movements during sleep. When administered centrally in rat, alpha-MSH and ACTH stimulate motor activity in wake, cause changes in sleep architecture, and increase periodic movements in sleep. These melanocortin hormones may play a role in the pathogenesis of RLS.