S20098 affects the free-running rhythms of body temperature and activity and decreases light-induced phase delays of circadian rhythms of the rat

Mammalian endogenous circadian rhythms are entrained to the environmental d ay-night cycle by light exposure. Melatonin is involved in this entrainment by signaling the day-night information to the endogenous circadian pacemak er. Furthermore, melatonin is known to affect the circadian rhythm of body temperature directly. A striking property of the endogenous melatonin signa l is its synthesis pattern, characterized by long-term elevated melatonin l evels throughout the night. In the present study, the influence of prolonge d treatment with the melatonin agonist S20098 during the activity phase of free-running rats was examined. This was achieved by giving S20098 in the f ood. The free-running body temperature and activity rhythms were studied. T he present study shows that enhancement of the melatonin signal, using S200 98, affected the free-running rhythm by gradual phase advances of the start of the activity phase, consequently causing an increase in length of the a ctivity phase. A well-known feature of circadian rhythms is its time-depend ent sensitivity for light. Light pulse exposure of an animal housed under c ontinuous dark conditions can cause a phase shift of the circadian pacemake r. Therefore, in a second experiment, the influence of melatonin receptor s timulation on the sensitivity of the pacemaker to light was examined by giv ing the melatonin agonist S20098 in the food during 1 day prior to exposure to a 60-min light pulse of 0, 1.5, 15, or 150 lux given at circadian time (CT) 14. S20098 pretreatment caused a diminished lightpulse-induced phase s hift when a light pulse of low light intensity (1.5 lux) was given. S20098 treatment via the food was sufficient to exert chronobiotic activity, and S 20098 treatment resulting in prolonged overstimulation of melatonin recepto rs is able to attenuate the effect of light on the circadian timing system.