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Emerging evidence has highlighted that the gut microbiota plays a critical role in the regulation of various aspects of mammalian physiology and behavior, including circadian rhythms. Circadian rhythms are fundamental behavioral and physiological processes that are governed by circadian pacemakers in the brain. Since mice are nocturnal, voluntary wheel running activity mostly occurs at night. This nocturnal wheel-running activity is driven by the primary circadian pacemaker located in the suprachiasmatic nucleus (SCN). Food anticipatory activity (FAA) is the increased bout of locomotor activity that precedes the scheduled short duration of a daily meal. FAA is controlled by the food-entrainable oscillator (FEO) located outside of the SCN. Several studies have shown that germ-free mice and mice with gut microbiota depletion altered those circadian behavioral rhythms. Therefore, this study was designed to test if the gut microbiota is involved in voluntary wheel running activity and FAA expression. To deplete gut microbiota, C57BL/6J wildtype mice were administered an antibiotic cocktail via their drinking water throughout the experiment. The effect of antibiotic cocktail treatment on wheel running activity rhythm in both female and male mice was not detectable with the sample size in our current study. Then mice were exposed to timed restricted feeding during the day. Both female and male mice treated with antibiotics exhibited normal FAA which was comparable with the FAA observed in the control group. Those results suggest that gut microbiota depletion has minimum effect on both circadian behavioral rhythms controlled by the SCN and FEO respectively. Our result contradicts recently published studies that reported significantly higher FAA levels in germ-free mice compared to their control counterparts and gut microbiota depletion significantly reduced voluntary activity by 50%.
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Overexpression of striatal D2 receptors reduces motivation thereby decreasing food anticipatory activity
Abstract Dopamine has been implicated in circadian timing underlying the food entrainable oscillator (FEO) circuitry and overexpression of the dopamine D2 receptor (D2R) in the striatum has been reported to reduce motivation to obtain food rewards in operant tasks. In the present study, we explored both of these mechanisms by examining food anticipatory activity (FAA) in dopamine D2 receptor‐overexpressing (D2R‐OE) mice under various durations of food availability. First, we noted that at baseline, there were no differences between D2R‐OEmice and their littermates in activity level, food intake, and body weight or in circadian activity. Under conditions of very restricted food availability (4 or 6 hr), both genotypes displayedFAA. In contrast, under 8‐hr food availability, control mice showedFAA, but D2R‐OEmice did not. Normalization of D2R by administration of doxycycline, a tetracycline analogue, rescuedFAAunder 8‐hr restricted food. We next tested for circadian regulation ofFAA. When given ad libitum access to food, neither D2R‐OEnor controls were active during the daytime. However, after an interval of food restriction, all mice showed elevated locomotor activity at the time of previous food availability in the day, indicating circadian timing of anticipatory activity. In summary, motivation is reduced in D2R‐OEmice but circadian timing behavior is not affected. We conclude that an increase in striatal D2R reducesFAAby modulating motivation and not by acting on a clock mechanism.
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- Award ID(s):
- 1749500
- PAR ID:
- 10080227
- Publisher / Repository:
- Wiley-Blackwell
- Date Published:
- Journal Name:
- European Journal of Neuroscience
- Volume:
- 51
- Issue:
- 1
- ISSN:
- 0953-816X
- Page Range / eLocation ID:
- p. 71-81
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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