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

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 (tau) of the SCN pacemaker is significantly lengthened by deuteriation. Sensitivity of food-entrained circadian rhythms to D(2)O (25% in drinking water) was evaluated in intact and SCN-ablated rats entrained to daily feeding schedules. In intact rats fed ad-libitum, D(2)O lengthened tau 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(2)O. 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(2)O intake. Transient delays and disruption of anticipatory activity were evident in intact and one partial SCN-ablated rat during D(2)O treatment, but these are interpretable as effects of coupling and/or masking interactions between a D(2)O-sensitive light-entrainable pacemaker, and a D(2)O-resistant food-entrained pacemaker. Differential sensitivity to D(2)O suggests diversity in the molecular mechanisms of food- and light-entrainable circadian pacemakers in mammals. D(2)O 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.