Circadian acclimatization of performance, sleep, and 6-sulfatoxymelatonin using multiple phase shifting stimuli.

Misalignment between the environment and one's circadian system is a common phenomenon (e.g., jet lag) which can have myriad negative effects on physical and mental health, mental and physiological performance, and sleep. Absent any intervention, the circadian system adjusts only 0.5-1.0 h per day to a shifted light-dark and sleep-wake schedule. Bright light facilitates circadian adjustment, but in field studies, bright light is only modestly better than no stimulus. Evidence indicates that exercise and melatonin can be combined with bright light to elicit larger shifts but no study has combined all of these stimuli or administered them at the times that are known to elicit the largest effects on the circadian system. The aims of this study are to compare the effects of different treatments on circadian adjustment to simulated jet lag in a laboratory. Following 2 weeks of home recording, 36 adults will spend 6.5 consecutive days in the laboratory. Following an 8 h period of baseline sleep recording on the participant's usual sleep schedule on Night 1 (e.g., 0000-0800 h), participants will undergo a 26 h circadian assessment protocol involving 2 h wake intervals in dim light and 1 h of sleep in darkness, repeated throughout the 26 h. During this protocol, all urine voidings will be collected; mood, sleepiness, psychomotor vigilance, and pain sensitivity will be assessed every 3 h, forehead temperature will be assessed every 90 min, and anaerobic performance (Wingate test) will be tested every 6 h. Following, the circadian assessment protocol, the participant's sleep-wake and light dark schedule will be delayed by 8 h compared with baseline (e.g., 0800-1400 h), analogous to travelling 8 times zones westward. This shifted schedule will be maintained for 3 days. During the 3 days on the delayed schedule, participants will be randomized to one of 3 treatments: (1) Dim Red Light + Placebo Capsules, (2) Bright Light Alone, (3) Bright Light + Exercise + Melatonin. During the final 26 h, all conditions and measures of the baseline circadian protocol will be repeated. Acclimatization will be defined by shifts in circadian rhythms of aMT6s, psychomotor vigilance, Wingate Anaerobic performance, mood, and sleepiness, and less impairments in these measures during the shifted schedule compared with baseline. We posit that Bright Light Alone and Bright Light + Exercise + Melatonin will elicit greater shifts in circadian rhythms and less impairments in sleep, mood, performance, and sleepiness compared with Dim Red Light + Placebo Capsules. We also posit that Bright Light + Exercise + Melatonin will elicit greater shifts and less impairments than Bright Light Alone.

Twice daily melatonin peaks in Siberian but not Syrian hamsters under 24 h light:dark:light:dark cycles.

The daily pattern of blood-borne melatonin varies seasonally under the control of a multi-oscillator circadian pacemaker. Here we examine patterns of melatonin secretion and locomotor activity in Siberian and Syrian hamsters entrained to bimodal LDLD8:4:8:4 and LD20:4 lighting schedules that facilitate novel temporal arrangements of component circadian oscillators. Under LDLD, both species robustly bifurcated wheel-running activity in distinct day scotophase (DS) and night scotophase (NS) bouts. Siberian hamsters displayed significant melatonin increases during each scotophase in LDLD, and in the single daily scotophase of LD20:4. The bimodal melatonin secretion pattern persisted in acutely extended 16 h scotophases. Syrian hamsters, in contrast, showed no significant increases in plasma melatonin during either scotophase of LDLD8:4:8:4 or in LD20:4. In this species, detectable levels were observed only when the DS of LDLD was acutely extended to yield 16 h of darkness. Established species differences in the phase lag of nocturnal melatonin secretion relative to activity onset may underlie the above contrast: In non-bifurcated entrainment to 24 h LD cycles, Siberian hamsters show increased melatonin secretion within ≈ 2 h after activity onset, whereas in Syrian hamsters, detectable melatonin secretion phase lags activity onset and the L/D transition by at least 4 h. The present results provide new evidence indicating multi-oscillator regulation of the waveform of melatonin secretion, specifically, the circadian control of the onset, offset and duration of nocturnal secretion.