Intrinsic activity rhythms in Macaca mulatta: their entrainment to light and melatonin

Abstract

Mounting evidence that circadian abnormalities are a risk factor for cancer and for cardiovascular, psychiatric, and other disorders calls for in-depth investigation of intrinsic clock-dependent processes in diurnal animal models phylogenetically close to humans. Rhesus monkey (Macaca mulatta) is the most extensively studied diurnal nonhuman primate. Similar to humans, it features consolidated nighttime sleep and advanced cardiovascular, neuroendocrine, and cognitive responses. However, the intrinsic circadian rhythmicity in this species remains to be fully characterized. Here it is demonstrated that under constant dim light (~10 lx) conditions, young adult rhesus monkeys maintain robust intrinsic circadian rhythms of activity, with periods ranging from 23.4 to 25.1 h. Constant environmental light of moderate intensity (~100 lx) slows down the circadian clock in rhesus monkeys. The exposure to light or melatonin shifts the phase of intrinsic circadian rhythms, with the direction and magnitude of the shift dependent on the circadian phase at which a stimulus was administered. The length of the intrinsic period largely defines an individual's chronotype (morningness or eveningness) and affects the stability of intrinsic rhythms and the phase angle of entrainment to melatonin and light. This first detailed characterization of intrinsic circadian rhythms of activity and their responses to light and melatonin in rhesus monkeys shows principal similarities to those in humans. These findings should provide new opportunities for translational research on the effects of diverse agents, environmental conditions, aging, and disease on the circadian clock and its outputs.