A Sex Difference in Circadian Food-Anticipatory Rhythms in Mice: Interaction With Dopamine D1 Receptor Knockout

Restricted daily feeding schedules induce circadian rhythms of food-anticipatory activity (FAA) in mice and other species. The entrainment pathway(s) and location(s) of circadian oscillators driving these rhythms have not been definitively established. An important role for dopamine signaling and the dorsal striatum is suggested by a confluence of observations, including shifting of FAA rhythms by dopamine receptor agonists and attenuation by antagonists and D1 receptor knockout (D1R KO). The dopamine reward system exhibits sexual dimorphisms in structure and function; if FAA rhythms are regulated by this system, then FAA may also be sexually dimorphic. To assess this prediction, disk running and general activity were recorded continuously in male and female C57BL/6J mice with food available ad libitum and then restricted to a 4-hr daily meal in the middle of the light period. Compared with male mice, FAA in female mice was significantly reduced in duration, total count, peak level, and ratio relative to nocturnal activity. To determine whether these differences were mediated by D1 receptors, male and female homozygous D1R KO mice were examined. Compared with wild type and heterozygous mice, female and male D1R KO mice exhibited a marked attenuation of FAA parameters. The magnitude of the attenuation was greater in female mice. These results confirm an important role for dopamine D1 receptors in the circadian mechanism by which mice anticipate a daily meal, and they reveal a previously unreported sexual dimorphism in the expression of food-anticipatory rhythms that is amplified by D1R KO.