Exploring the role of locomotor sensitization in the circadian food entrainment pathway

Abstract

Food entrainment is the internal mechanism whereby the phase and period of circadian clock genes comes under the control of daily scheduled food availability. Food entrainment allows the body to efficiently realign the internal timing of behavioral and physiological functions such that they anticipate food intake. Food entrainment can occur with or without caloric restriction, as seen with daily schedules of restricted feeding (RF) or restricted treat (RT) that restrict food or treat intake to a single feeding time. However, the extent of clock gene control is more pronounced with caloric restriction, highlighting the role of energy balance in regulating clock genes. Recent studies have implicated dopamine (DA) to be involved in food entrainment and caloric restriction is known to affect dopaminergic pathways to enhance locomotor activity. Since food entrainment results in the development of a distinct behavioral component, called food anticipatory activity (FAA), we examined the role of locomotor sensitization (LS) in food entrainment by 1) observing whether amphetamine (AMPH) sensitization results in enhanced locomotor output of FAA and 2) measuring LS of circadian and non-circadian feeding paradigms to an acute injection of AMPH (AMPH cross-sensitization). Unexpectedly, AMPH sensitization did not show enhancement of FAA. On the contrary, LS did develop with sufficient exposure to RF. LS was present after 2 weeks of RF, but not after 1, 3 or 7 days into RF. When food was returned and rats regain their original body weight at 10–15 days post-RF, LS remained present. LS did not develop to RT, nor to feedings of a non-circadian schedule, e.g. variable restricted feeding (VRF) or variable RT (VRT). Further, when RF was timed to the dark period, LS was observed only when tested at night; RF timed to the light period resulted in LS that was present during day and night. Taken together our results show that LS develops with food entrainment to RF, an effect that is dependent on the chronicity and circadian phase of RF but independent of body weight. Given that LS involves reorganization of DA-regulated motor circuitry, our work provides indirect support for the role of DA in the food entrainment pathway of RF. The findings also suggest differences in neuronal pathways involved in LS from AMPH sensitization and LS from RF.

Overexpression of striatal D2 receptors reduces motivation thereby decreasing food anticipatory activity

“…We found that FAA activity was higher in the Dox condition than in the comparable 8‐hr RF condition (mean of ~2000 for RF8 vs. ~3000 wheel rotations at the end of Dox treatment). This is consistent with reports that locomotor sensitization develops with sufficient exposure to RF (Opiol et al., ).…”

Control of exploration, motor coordination and amphetamine sensitization by cannabinoid CB1 receptors expressed in medium spiny neurons

“…Behavioural sensitization to amphetamine is expressed as a progressive enhancement of locomotion with repeated amphetamine injections. In mice, CB 1 R are involved in the induction of AS (Corbillé et al, 2007) and can be measured by the long‐lasting hypersensitivity to its stimulatory effect on locomotion (Opiol et al, 2017; Richetto et al, 2013; Vezina & Stewart, 1989). Figure 7e shows that CB 1 R (MSN) mice displayed similar AS compared with WT, whereas CB 1 R KO mice did not exhibit significant AS.…”

Reversal of obesity: the quest for the optimum dietary regimen

“…Caloric restriction, and also presumably TRF, have a strong impact on food entrainment, which appears to influence dopaminergic pathways which enhance locomotor sensitisation. [159] Studies show that in animals with diet induced Interestingly, fewer participants withdrew from TRF studies relative to intermittent fasting studies. [161] Other studies have shown that TRF in humans can increase brown adipose tissue at the expense of white, as well as synchronising circadian rhythms and metabolism, although the mechanism for this is not yet understood.…”