A sex difference in circadian food-anticipatory rhythms in mice: Interaction with dopamine D1 receptor knockout.

Abstract

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.

Sex differences in circadian food anticipatory activity are not altered by individual manipulations of sex hormones or sex chromosome copy number in mice

“…A study from our laboratory of FAA induced by scheduled palatable meals showed that males expressed moderate FAA in response to timed delivery of fatty meals whereas females did not [ 8 ]. More recently, sex differences in FAA to time restricted feeding (negative energy balance conditions) were independently confirmed in two laboratories [ 9 , 10 ]. Michalik and colleagues found an additive effect of deletion of dopamine receptor 1 and female sex on weakening FAA [ 10 ].…”

“…A sexual dimorphism in FAA could help to indicate the underlying neuronal circuitry behind the food entrained oscillator(s) given that the male and female brain show only a handful of anatomical differences [ 7 ]. Recently, evidence for biological sex differences in circadian entrainment to scheduled feeding has emerged [ 8 – 10 ]. In all of these studies, female mice showed a blunted behavioral response to scheduled feeding as compared to males, which showed higher amplitudes of FAA and more rapid entrainment.…”

The Running Wheel Enhances Food Anticipatory Activity: An Exploratory Study

“…For example, FAA was attenuated when the core of the nucleus accumbens was chemically lesioned in rats (Mendoza et al, 2005b ). In addition, FAA was attenuated by inhibition of dopaminergic signaling via treatment with D1 or D2 receptor antagonists (Liu et al, 2012 ) and in D1 receptor knockout mice (Gallardo et al, 2014 ; Michalik et al, 2015 ). It has also been reported that mu-opioid receptor knockout mice display attenuated FAA when feeding is restricted to 3 h during the night (Kas et al, 2004 ), suggesting that endogenous opioids influence the robustness of FAA.…”

“…Recent studies show that dopamine and opioids, which are important components of the reward pathway, regulate the robustness of FAA (Kas et al, 2004 ; Mendoza and Challet, 2014 ). FAA is attenuated in D1 receptor, but not D2 receptor, knockout mice (Gallardo et al, 2014 ; Michalik et al, 2015 ). Systemic pre-treatment (before the onset of food) with D1 and D2 receptor antagonists attenuated FAA in ICR mice (Liu et al, 2012 ).…”

Sincronização fótica e não fótica dos ritmos circadianos em roedores subterrâneos (Ctenomys aff. knighti) e roedores modelo de laboratório (Mus musculus)

“…It is proposed that FAA is regulated by a self-sustaining circadian oscillator or oscillators outside the SCN (Figure 3.1), the food entrainable oscillator(s) (FEO) (Mistlberger, 1994;Stephan, 2002). Despite the great number of studies on different central and peripheral structures, the anatomical locus of the FEO is still unknown (reviewed in Davidson, 2009;Mistlberger, 2011;Patton and Mistlberger, 2013 (Gallardo et al, 2014;Michalik et al, 2015). Failure to identify a single structure indicate that the FEO may be a network of widespread oscillators that together mediate food entrainment.…”