Food-entrained circadian rhythms in rats are insensitive to deuterium oxide

Abstract

Rats anticipate a scheduled daily meal by entrainment of a circadian pacemaker separate from the light-entrainable circadian pacemaker located in the suprachiasmatic nuclei (SCN). The site and molecular mechanisms of the food-entrainable pacemaker are unknown. The intrinsic period ( τ) of the SCN pacemaker is significantly lengthened by deuteriation. Sensitivity of food-entrained circadian rhythms to D 2O (25% in drinking water) was evaluated in intact and SCN-ablated rats entrained to daily feeding schedules. In intact rats fed ad-libitum, D 2O lengthened τ sufficiently to drive activity rhythms out of entrainment to the light–dark cycle. By contrast, food-entrained rhythms were surprisingly resistant to modulation by D 2O. The mean daily onset time of food anticipatory activity in rats with complete SCN-ablations was not affected by up to 28 days of D 2O intake. Transient delays and disruption of anticipatory activity were evident in intact and one partial SCN-ablated rat during D 2O treatment, but these are interpretable as effects of coupling and/or masking interactions between a D 2O-sensitive light-entrainable pacemaker, and a D 2O-resistant food-entrained pacemaker. Differential sensitivity to D 2O suggests diversity in the molecular mechanisms of food- and light-entrainable circadian pacemakers in mammals. D 2O may have utility as a screening test to identify putative food-entrainable pacemakers from among those central and peripheral tissues that can express circadian oscillations of clock genes independent of the SCN.