MELATONIN-INDUCED TEMPERATURE SUPPRESSION AND ITS ACUTE PHASE-SHIFTING EFFECTS CORRELATE IN A DOSE-DEPENDENT MANNER IN HUMANS

Melatonin is able to phase-shift the endogenous circadian clock and ca n induce acute temperature suppression. It is possible that there is a direct relationship between these phenomena. In a double-blind, place bo-controlled crossover study, 6 healthy volunteers maintained a regul ar sleep/wake cycle in a normal environment. From dusk until 24:00 h o n days (D) 1-4 subjects remained in dim artificial lighting(< 50 lux) and darkness(< 1 lux) from 24:00-08:00 h. At 17:00 h on D3 either mela tonin (0.05 mg, 0.5 mg or 5 mg) or placebo was administered. Melatonin treatment induced acute, dose-dependent temperature suppression and d ecrements in alertness and performance efficiency. On the night of D3, earlier sleep onset, offset and better sleep quality were associated with increasing doses of melatonin. The following day, a significant d ose-dependent phase-advance in the plasma melatonin onset time and tem perature nadir (D4-5) was observed with a trend for the alertness rhyt hm to phase-advance. A significant dose-response relationship existed between the dose of oral melatonin, the magnitude of temperature suppr ession and the degree of advance phase shift in the endogenous melaton in and temperature rhythms, suggesting that acute changes in body temp erature by melatonin may be a primary event in phase-shifting mechanis ms.