Melatonin advances the circadian timing of EEG sleep and directly facilitates sleep without altering its duration in extended sleep opportunities in humans

被引:113
作者
Rajaratnam, SMW
Middleton, B
Stone, BM
Arendt, J
Dijk, DJ
机构
[1] Monash Univ, Sch Psychol Psychiat & Psychol Med, Clayton, Vic 3800, Australia
[2] Univ Surrey, Sch Biomed & Mol Sci, Guildford GU2 5XH, Surrey, England
来源
JOURNAL OF PHYSIOLOGY-LONDON | 2004年 / 561卷 / 01期
关键词
D O I
10.1113/jphysiol.2004.073742
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The rhythm of plasma melatonin originating from the pineal gland and driven by the circadian pacemaker located in the suprachiasmatic nucleus is closely associated with the circadian (approximately 24 h) variation in sleep propensity and sleep spindle activity in humans. We investigated the contribution of melatonin to variation in sleep propensity, structure, duration and EEG activity in a protocol in which sleep was scheduled to begin during the biological day, i.e. when endogenous melatonin concentrations are low. The two 14 day trials were conducted in an environmental scheduling facility. Each trial included two circadian phase assessments, baseline sleep and nine 16 h sleep opportunities (16.00-08.00 h) in near darkness. Eight healthy male volunteers (24.4 +/- 4.4 years) without sleep complaints were recruited, and melatonin (1.5 mg) or placebo was administered at the start of the first eight 16 h sleep opportunities. During melatonin treatment, sleep in the first 8 h of the 16 h sleep opportunities was increased by 2 h. Sleep per 16 h was not significantly different and approached asymptotic values of 8.7 h in both conditions. The percentage of rapid eye movement (REM) sleep was not affected by melatonin, but the percentage of stage 2 sleep and sleep spindle activity increased, and the percentage of stage 3 sleep decreased. During the washout night, the melatonin-induced advance in sleep timing persisted, but was smaller than on the preceding treatment night and was consistent with the advance in the endogenous melatonin rhythm. These data demonstrate robust, direct sleep-facilitating and circadian effects of melatonin without concomitant changes in sleep duration, and support the use of melatonin in the treatment of sleep disorders in which the circadian melatonin rhythm is delayed relative to desired sleep time.
引用
收藏
页码:339 / 351
页数:13
相关论文
共 60 条
[1]   A longer biological night in long sleepers than in short sleepers [J].
Aeschbach, D ;
Sher, L ;
Postolache, TT ;
Matthews, JR ;
Jackson, MA ;
Wehr, TA .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2003, 88 (01) :26-30
[2]   Melatonin receptor subtype expression in human cerebellum [J].
Al-Ghoul, WM ;
Herman, MD ;
Dubocovich, ML .
NEUROREPORT, 1998, 9 (18) :4063-4068
[3]   Melatonin, circadian rhythms, and sleep [J].
Arendt, J .
NEW ENGLAND JOURNAL OF MEDICINE, 2000, 343 (15) :1114-1116
[4]  
ARENDT J, 1985, CIBA F SYMP, V117, P266
[5]   MELATONIN PHASE ADVANCES CIRCADIAN-RHYTHM [J].
ATTENBURROW, MEJ ;
DOWLING, BA ;
SARGENT, PA ;
SHARPLEY, AL ;
COWEN, PJ .
PSYCHOPHARMACOLOGY, 1995, 121 (04) :503-505
[6]   Sleep and 24 hour body temperatures: a comparison in young men, naturally cycling women and women faking hormonal contraceptives [J].
Baker, FC ;
Waner, JI ;
Vieira, EF ;
Taylor, SR ;
Driver, HS ;
Mitchell, D .
JOURNAL OF PHYSIOLOGY-LONDON, 2001, 530 (03) :565-574
[7]   Phototransduction by retinal ganglion cells that set the circadian clock [J].
Berson, DM ;
Dunn, FA ;
Takao, M .
SCIENCE, 2002, 295 (5557) :1070-1073
[8]   Daytime melatonin administration enhances sleepiness and theta/alpha activity in the waking EEG [J].
Cajochen, C ;
Krauchi, K ;
vonArx, MA ;
Mori, D ;
Graw, P ;
WirzJustice, A .
NEUROSCIENCE LETTERS, 1996, 207 (03) :209-213
[9]   EEG and ocular correlates of circadian melatonin phase and human performance decrements during sleep loss [J].
Cajochen, C ;
Khalsa, SBS ;
Wyatt, JK ;
Czeisler, CA ;
Dijk, DJ .
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 1999, 277 (03) :R640-R649
[10]   Melatonin and S-20098 increase REM sleep and wake-up propensity without modifying NREM sleep homeostasis [J].
Cajochen, C ;
Krauchi, K ;
Mori, D ;
Graw, P ;
WirzJustice, A .
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 1997, 272 (04) :R1189-R1196